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 Chilling Effects Clearinghouse > DMCA Notices > Notices > Article DMCA (Copyright) Complaint to Google (NoticeID 134671, http://chillingeffects.org/N/134671) Printer-friendly version

Article DMCA (Copyright) Complaint to Google

September 15, 2011

 

Sender Information:
Manuka Natural Ltd.
Sent by:



NZ

Recipient Information:

Google, Inc.


Mountain View, CA, 94043, USA


Sent via: online form
Re: Websearch Infringement Notification via Online Form Complaint

Google DMCA Form: Infringement Notification for Web Search

Contact Information
Name: [redacted]
Company Name: Manuka Natural Ltd.
Copyright holder: Manuka Natural Ltd.
Country/Region: NZ

YOUR COPYRIGHTED WORK

Copyright claim #0:
  Cellulitis Protection


New Zealand Manuka oil and UMF® honey are proven in scientific studies to be strongly antibacterial, antifungal, and anti-inflammatory, providing effective natural protection against Cellulitis infection.

Cellulitis should not be confused with cellulite which is caused by fat deposits below the skin causing a dimpling appearance.

Cellulitis is a bacterial infection of the skin affecting both the outer layer of the skin and the deep subcutaneous tissue below the skin, caused mainly by the presence of Staphylococcus and Streptococcus bacteria. It will most commonly infect exposed areas of the body such as the lower legs, feet, arms and face. It can be common in elderly people, diabetics and people with lowered immune systems, causing poor blood circulation and leading to ulcers of the lower legs and feet.

Cellulitis infection is also very common amongst dense populations where hygiene facilities are shared, and include gymnasiums, rest homes, swimming pools and military installations.

Anything which results in damage to the skin can trigger the onset of Cellulitis, incidents such as chickenpox, shingles, insect or animal bites, surgery, eczema, burns or boils, can be the entry point and opportunity for the bacteria to spread and multiply.

The initial signs of a Cellulitis infection will be redness, warmth, pain and tenderness of the infected area which may be accompanied by fever, headache and nausea.

Once the bacteria become established below the skin, a very serious infection can result by entering the lymph nodes and bloodstream, and spreading throughout the body.

If allowed to get to this stage Cellulitis can require oral or intravenous antibiotics and hospitalization, and a medical practitioner should be consulted immediately.

It is vital that people in any of the ‘at risk’ groups take great care of their skin, and treat any area of skin damage immediately with a topical antibiotic to prevent escalation of the infection.

Treatment:

One of the best natural topical antibiotics is Manuka UMF® honey, applied either directly and covered with gauze, or as a cream. Manuka essential oil in diluted form or as a cream is also highly effective.

Both Manuka UMF® honey and essential oil have been proven in scientific studies to completely eliminate even the most persistent Methicillin-resistant Staphylococcus aureus (MRSA) bacteria, (a major cause of Cellulitis) which is resistant to many of the synthetic antibiotics.

MRSA has become such a serious problem in many hospitals and clinics around the world that natural compounds have undergone extensive study, with Manuka extracts having been found to be one of the most effective ways of eliminating the Methicillin-resistant Staphylococcus aureus bacteria.

The following Manuka essential oil and Manuka UMF® honey products offer a natural alternative for protection against Cellulitis infection, and in many cases, may provide superior results;

Manuka UMF® Honey, 15+ or 20+

HoneyManuka UMF® Honey Cream (containing Manuka oil and 30% Manuka UMF® honey)

Manu Strong Manuka oil (25% Manuka oil)

East Cape Manuka Cream (4% Manuka oil)

Manu Manuka Soap (1.5% Manuka oil)

Recommendation for use:

Apply any of the products listed above immediately to any area of skin trauma, (even to the smallest scratch, or insect bite) repeat after 2-4 hours and thereafter twice daily until the area is fully healed, use the Manuka soap for washing affected areas as required.

Quantity to order:

People who are in an ‘at risk’ group and who could be susceptible to Cellulitis infection, should have a selection of Manuka products available for immediate use, as the time delay between ordering products and applying them to the skin could result in a more serious development of an infection.

Because Cellulitis infection can in extreme cases be life threatening, it is vital to treat any damaged skin without delay to prevent further infection, if redness, swelling or nausea continues, consult a medical practitioner immediately.

Important health benefits from using natural remedies Manuka oil is a natural compound found in nature that is not chemically altered in any way. No adverse side effects have ever been reported from the use of Manuka honey or oil products. Manuka oil will safely and effectively control most strains of bacteria that can cause Cellulitis.

Manuka UMF® Honey is not chemically altered in any way, it is highly anti-bacterial in its natural form, and is known to penetrate deeply into the epidermis, greatly assisting the control of bacterial infection. It is important to remember that everything that you apply to your skin is absorbed into your body, so by using natural products you can enjoy a healthier and happier life by eliminating the use of products that could have harmful side effects. To order, click on an individual product below, or for the full selection click here
Original work URL(s):
  http://www.manukanatural.com/pages/Cellulitis-Protection.html

Allegedly infringing URLs:

Copyright claim #1:
  East Cape Manuka Oil



Active anti-microbial properties of ‘Tea Tree' oils show wide variation between species and within species at different locations.

Manuka, Kanuka and Australian Tea Tree are wild plants that grow naturally throughout New Zealand and Southern Australia, and which can be broadly divided into the following groups:

New Zealand Tea Tree or Manuka (Leptospermum scoparium)
New Zealand Kanuka (Kunzea ericoides, formerly Leptospermum ericoides)
Australian Tea Tree (Melaleuca alternifolia)

All these species contain oils which have generally been referred to as Tea Tree oil.

For more than two centuries there has been anecdotal evidence supporting the ability of this group of tea tree oils to provide relief from various bacterial and fungal skin complaints.

Recently however, there has been considerable research undertaken to verify the effectiveness of New Zealand tea tree or Manuka oil, compare it with other Tea Tree oils, and to identify which chemotype within the Manuka species is most active against a number of organisms.

Four major chemotypes were found to be present in New Zealand tea tree Manuka oil.

They are Monoterpene rich oils, Sesquiterpene rich oils, Triketone enriched oils and Methyl Cinnamate enriched oils.

The Triketone rich oils occur only in the East Cape region of the North Island of New Zealand

Furthermore, the Triketone levels in the East Cape Manuka oil were found to be four to five times higher than the average of the oils collected from other locations in the North Island.

What is greatly significant about the Triketone chemotype is that this compound is highly effective against a number of gram positive bacteria and fungi.

This specific East Cape Manuka oil has also been shown to be up to 30 times more effective against gram positive bacteria than Australian Tea Tree oils.

References:
In a study to ‘Define North Island Manuka Chemotype Resources' undertaken in 2001 by M. Douglas, R. Anderson, J. van Klink, N. Perry and B. Smallfield, four major chemotypes were found to be present in New Zealand Manuka oil in foliage collected and analysed from 132 plants from 44 sites throughout the North Island.

Dr. Noel Porter, Crop & Food Research Lincoln, Dr. Jeff Reid, Crop & Food Research Hawke's Bay.

Superior antimicrobial effectiveness of East Cape Manuka Chemotype

The active ingredient that is highly effective against gram positive bacteria and fungi is the Triketone rich chemotype containing Leptospermone, Iso-leptospermone and Flavesone. These natural compounds are present in East Cape Manuka Oil at concentrations of 25 to 30 %. (Determined by % peak area of GC-FID)

This Manuka oil from the East Cape region of New Zealand has been found to be more active than any other Tea Tree oil against pathological bacteria e.g. Staphylococcus, Listeria, Enterococcus, and some fungi e.g. Trichophyton and Microsporum as well as having anthelmintic (internal parasite) and insecticidal activities.

The unique activity of the East Cape Manuka oils against gram positive bacteria e.g. Staphylococcus Aureus and its antibiotic resistant strain MRSA has been conclusively proven to be due to the presence of Triketones in the East Cape Manuka oil.

Note: it is vitally important to understand that while other Manuka and Tea Tree oils may exhibit some therapeutic qualities, only the Triketone rich Manuka oil from the East Cape region of New Zealand will be effective against the bacteria and fungi in the recommended concentrations described in the scientific studies on this website.

Production and harvesting restricted by topography and plant characteristics

While Manuka, Kanuka and Tea Tree plants are widely distributed throughout New Zealand and Southern areas of Australia, the geographical area which produces Triketone rich Manuka oil is relatively small, often includes steep hillsides and is remote geographically.

Because the Manuka plant grows in the wild, and is not cultivated in commercial plantations it is not sprayed with chemicals nor is its growth stimulated with chemical fertilizers.

In this sense it can be considered to be grown organically, although it is probably more accurate to describe it as ‘collected from the wild'.

To ensure continuing production of the resource, only small quantities of leaf material can be harvested from each plant, and it can only be harvested every second year.

Studies continue into selection of superior plant material for propagation and establishment in plantations. However there is wide variation between individual plants in both growth habit and oil production, further compounded by the slow growth of the species.

Therefore commercial production from plantations of Manuka is considered to be many years in the future.

Steam distillation method used to extract Manuka oil

To produce Manuka Essential oil, young foliage is cut from the Manuka bushes and shrubs in the wild populations, bagged and taken to the distillation plant.

There it is chopped and compressed into cartridges that are loaded into the still pot. The oil is then extracted by passing steam through the plant material.

Because the Triketone rich oils of the East Cape Manuka chemotype are less volatile than other Tea Tree oils, steam extraction takes up to five hours.

Once the oil is separated from the plant material by the steam, it is cooled so that it returns to liquid. The distillation equipment must be carefully adjusted to achieve the best compromise between good oil yields and high extraction costs.

Smaller commercial quantities and a longer production process inevitably lead to higher production costs so this special Triketone rich oil is more expensive than other more abundant, more accessible and more easily extracted Manuka and ‘Tea Tree' oils.

The unique and proven characteristics of this Triketone rich oil make it highly sought after as a pure oil and for inclusion in healing creams and cosmetics, putting further pressure on the supply and demand equation.

When you purchase Manuka or Tea Tree oil skin care products, if you want the highest levels of antimicrobial activity, you should check that the oil is sourced from the East Cape region of the North Island, New Zealand.

Products containing tea tree oil from other species or locations should always be cheaper on a volume basis, but in terms of active ingredient (Triketones), they are more expensive and a lot less effective.
Original work URL(s):
  http://www.manukanatural.com/pages/East-Cape-Manuka-Oil.html

Allegedly infringing URLs:
  0.   http://www.lesfloralies.co.nz/manuka_oil_information.htm

Copyright claim #2:
  East Cape Manuka Tea Tree Oil Effectivness


Scientific studies demonstrate New Zealand East Cape Manuka essential oil to be highly effective against a range of bacteria and fungi even at very low concentrations

The Cawthron Institute testing showed NZ East Cape Manuka oil to be active against a wide range of micro-organisms that cause irritation and infection of the skin and body.

Some of these bacterial micro-organisms are serious such as MRSA (more commonly known as the H-bug) while others are more common, such as fungi which cause Athletes foot.

The Cawthron Institute concluded that East Cape Manuka tea tree oil was 20 - 30 times more active than Australian tea tree oil against gram positive bacteria. Further testing has confirmed that East Cape Manuka tea tree oil is effective in combating bacteria including those associated with acne, and combating fungi that cause Tinea (Athletes foot), foot and body odour.

Comparison of effectiveness of NZ East Cape Manuka tea tree oil and Australian tea tree oil against selected bacteria

Please Note: The graphs shown here are expressed in minimum inhibitory concentration (MIC) (ie the lowest concentration which will inhibit the growth of a specified organism) therefore the shorter the bars are on the chart, the more effective the product will be in controlling the organism.

PRODUCT NAME: Manuka Oil
INCI NAME: Leptospermum Scoparium Oil
TRADENAMES: Tairawhiti Manuka Oil, Manex Oil

TAIRAWHITI (EAST CAPE) MANUKA OIL has been independently tested against a wide range of organisms and has been found to be active against all of those tested.

The minimum inhibitory concentration (MIC) (ie the lowest concentration which will inhibit the growth of a specified organism) was determined. A list of some of these follows:


Organism. MIC (% w/v) Gram
Positive Bacteria - (liquid culture method)


Staphyloccocus
Aureas 147

0.078


Staphyloccocus
Aureas MRSA NS

0.020


Staphyloccocus
epidermis

0.078


Staphyloccocus
faecalis

0.039


Staphyloccocus
agalactiae

0.039


Micrococcus
luteus

0.020


Sarcina
lutea

0.078


Bacillus
subtilis

0.156


Listeria
monocytogenes

0.039
Original work URL(s):
  http://www.manukanatural.com/pages/East-Cape-Manuka-Tea-Tree-Oil-Effectivness--.html

Allegedly infringing URLs:

Copyright claim #3:
  Gram Positive Bacteria Scientific Studies


Scientific studies demonstrate New Zealand East Cape Manuka essential oil to be highly effective against a range of bacteria and fungi even at very low concentrations

The Cawthron Institute testing showed NZ East Cape Manuka oil to be active against a wide range of micro-organisms that cause irritation and infection of the skin and body.

Some of these bacterial micro-organisms are serious such as MRSA (more commonly known as the H-bug) while others are more common, such as fungi which cause Athletes foot, Ringworm, Jock itch and Seborrheic dermatitis.

The Cawthron Institute concluded that East Cape Manuka oil was 20 - 30 times more active than Australian tea tree oil against gram positive bacteria. Further testing has confirmed that East Cape Manuka oil is effective in combating bacteria including those associated with acne, and combating fungi that cause Tinea (Athletes foot), foot and body odour.

Comparison of effectiveness of NZ East Cape Manuka oil and Australian tea tree oil against selected bacteria

Please Note: The graphs shown here are expressed in minimum inhibitory concentration (MIC) (ie the lowest concentration which will inhibit the growth of a specified organism) therefore the shorter the bars are on the chart, the more effective the product will be in controlling the organism.

PRODUCT NAME: Manuka Oil
INCI NAME: Leptospermum Scoparium Oil
TRADENAMES: Manu Manuka oil

The minimum inhibitory concentration (MIC) (ie the lowest concentration which will inhibit the growth of a specified organism) was determined. A list of some of these follows:





Organism. MIC (% w/v) Gram Positive Bacteria - (liquid culture method)


Staphyloccocus Aureas 147

0.078


Staphyloccocus Aureas MRSA NS

0.020


Staphyloccocus epidermis

0.078


Staphyloccocus faecalis

0.039


Staphyloccocus agalactiae

0.039


Micrococcus luteus

0.020


Sarcina lutea

0.078


Bacillus subtilis

0.156


Listeria monocytogenes

0.039
Original work URL(s):
  http://www.manukanatural.com/pages/Gram-Positive-Bacteria-Scientific-Studies.html

Allegedly infringing URLs:

Copyright claim #4:
  History Of Manuka Oil Use


Oral and written history of New Zealand records the use of Manuka for medicinal purposes by the early Maori settlers up to 1000 years ago.


From the earliest human habitation of New Zealand by the Maori people around 800 to 1000 years ago, the Manuka plant (Leptospermum scoparium) was known to have special medicinal and therapeutic properties.

The Maori people used the leaves and bark for a wide range of ailments, including urinary problems and as a febrifuge (to reduce fever).

The leaves were boiled and the hot vapour inhaled for head colds. Leaves and bark were boiled together and the warm liquid rubbed on stiff backs and rheumatic joints.

It was also used as a diuretic, a sedative, a painkiller, for inflammation of the breasts, and for healing fractures.

Boiled bark was used to relieve constipation, as a gargle and for bathing sore eyes. The emollient gum was given to suckling babies, and was applied to scalds and burns.

Fresh sap was taken as a blood purifier, seed capsules were boiled and the fluid used externally for bruises and inflammation, and internally for diarrhoea and dysentery.

Raw seed capsules were chewed for colic, and when powdered, used in a poultice to dry and heal open wounds or running sores.

“New Zealand Medicinal Plants” written by S C Brooker, R C cambie, R C Cooper. Published by Heineman Publishers, Auckland, NZ. Third Edition, 1987.

“Medicine of the Maori written by Christina McDonald. Published by William Collins (NZ) Ltd, Auckland, 1974. Reprinted.1975


It is amazing to discover that all these therapeutic uses of the Manuka plant were identified by the Maori people centuries ago, and only now, in the past two decades, has modern science shown that these uses were legitimate and that the active compounds have been identified and their efficacy confirmed in scientific analysis.

Captain James Cook discovers benefits from using Manuka leaves

Captain James Cook first visited New Zealand in 1769 and described the Manuka plant as a ‘tea plant’ hence the colloquial name tea tree.

Cook wrote: “…the leaves were used by many of us as a tea which has a very agreeable bitter taste and flavour when they are recent but loses some of both when they are dried. When the infusion was made strong it proved emetic (induced vomiting) to some in the same manner as ‘green tea’”

Cook, J “A Voyage Towards the South Pole and Round the World”. Strahan & Cadell, London, 1777

During the following two centuries since Cook wrote about Manuka in his journal, little more information of scientific nature was published.

Modern scientific study confirms medicinal properties

However since the 1980’s there has been considerable scientific study to identify the active compounds in this plant genus and test these compounds for their effectiveness against a number of bacterial and fungal organisms that can cause skin ailments.

It has been described in scientific papers that one variety of Manuka tea tree, grown almost exclusively in the East Cape region of New Zealand’s North Island, has significant antibacterial and antifungal properties and that this oil is a genuine alternative to conventional synthetic forms of medication.

Not only are products containing high Triketone Manuka oil an alternative to traditional forms of treatment, it has been shown in many cases to have given superior results.

Further confirmation of the therapeutic properties of Manuka honey can be found in the sections on Scientific Studies and Manuka Honey in Medicine.
Original work URL(s):
  http://www.manukanatural.com/pages/History-Of-Manuka-Oil-Use.html

Allegedly infringing URLs:
  0.   http://thehoneybear.co.za/manuka.htm

Copyright claim #5:
  Manuka Honey Research Abstracts



Allen, K. L., Molan P.C. & Reid G.M. (1991). "A survey of the antibacterial activity of some New Zealand honeys." Journal Of Pharmacy and Pharmacology 43(12), 817-822.

Abstract. To assess the variation in antibacterial activity of honey a survey was carried out on 345 samples of unpasteurized honey obtained from commercial apiarists throughout New Zealand.

Most of the honeys were considered to be monofloral, from 26 different floral sources. The honeys were tested against Staphylococcus aureus in an agar well diffusion assay, with reference to phenol as a standard. Antibacterial activity was found to range from the equivalent of less than 2% (w/v) phenol to 58% (w/v) phenol, with a median of 13.6 and a standard deviation of 12.5.

Neither the age of the honey samples nor whether they had been processed by the apiarist was associated with lower activity. However, the difference between floral sources in the antibacterial activity was very highly significant. Kanuka (Kunzea ericoides (A. Rich.) J. Thompson. Family: Myrtaceae), manuka (Leptospermum scoparium J. R. et G. Forst. Family: Myrtaceae), ling heather (Calluna vulgaris (L.) Hull. Family: Ericaceae) and kamahi (Weinmannia racemosa Linn. f. Family: Cunoniaceae) were shown to be sources likely to give honey with high antibacterial activity. When antibacterial activity was assayed with catalase added to remove hydrogen peroxide, most of the honeys showed no detectable antibacterial activity.

Only manuka and vipers bugloss (Echium vulgare L. Family: Boraginaceae) honeys showed this type of activity in a significant proportion of the samples. The high antibacterial activity of manuka honey was in many cases due entirely to this non-peroxide component.

Betts, J.A. & Molan, P.C. (2002) "Results of a pilot trial of manuka honey as a dressing for infected chronic wounds." - a paper presented at the 4th Australian Wound Management Association Conference, Adelaide, Australia.

Bignall J. (2003) "Honey & Heliobacter" The Lancet 342(8875), 858.

Brady N.F., Molan P.C. & Harfoot C.G. (1996) "The Sensitivity of Dermatophytes to the Anti-Microbial Activity of Manuka Honey & Other Honey." Pharm. Sciences 2(10), 471-473.

Abstract. Honey has been reported to have anti-fungal activity and so was tested against clinical isolates of the common dermatophyte species which cause tineas in man. A honey with an average level of hydrogen peroxide and a manuka (Leptospermum scoparium J.R. & G. Forst, Fam. Myrtaceae) honey with an average level of non-peroxide antibacterial activity were used. An agar well diffusion assay was used, the contents of the wells being replaced with freshly prepared honey solutions at 24h intervals over 3-4 days of incubation.

The lowest concentrations (% v/v, in steps of 5%) of manuka honey with catalase added to remove hydrogen peroxide, and of the other honey (without catalase) showed that the inhibition of growth around the walls were, repectively Epidermophyton floccosum 25%,10%, Microsporum canis 25%,15%, Microsporum gypseum 55%, 20%, Trichophyton mentagrophytes var. interdigitale 45%, 15%, Trichophyton mentagrophytes var. mentagrophytes 25%,15%, Trichophyton rubrum 20%, 5%, Trichophyton tonsurans 25%, 20%.

No inhibitory activity was detected with the other honey at 50% (v/v) with catalase added.

The results of this investigation show that the common dermatophytes are sensitive to the antimicrobial activity of honey, indicating that clinical evaluation of honey in the treatment of tineas is warranted. This would determine whether the hydrogen peroxide or the non-peroxide antifungal agent diffuses better into the skin.

Casey G. & van Rij A. (1997) "Manuka honey & leg ulcers." New Zealand Med. J. 110(1045), 216.

Chambers J. (2006). "Topical manuka for MRSA-contaminated skin ulcers." Palliat Med. 20(5), 557.

Cooper R.A. & Molan P.C. (1999). "The use of honey as an antiseptic in managing Pseudomonas infection." J. Wound Care 8(4), 161-164.

Abstract. A laboratory study was undertaken to extend existing knowledge about the effectiveness of the antibacterial properties of honey against pseudomonads. To date, sensitivity testing has used non-standardised honeys, which may vary greatly in their antibacterial potency.

Pure cultures of Pseudomonas spp, isolated from swabs from 20 infected wounds, were inoculated on the surface of nutrient agar plates containing various concentrations of honey in the medium. Two types of honey were used, a manuka honey and a pasture honey, each selected to have antibacterial activity close to the median for each type.

The minimum inhibitory concentration of the manuka honey for the 20 isolates ranged from 5.5-8.7% (v/v) (mean 6.9% (v/v), standard deviation 1.3). The minimum inhibitory concentration of the pasture honey for the 20 isolates ranged from 5.8-9.0% (v/v) (mean 7.1% (v/v), standard deviation 1.0).

Honeys with an average level of antibacterial activity could be expected to be effective in preventing the growth of pseudomonads on the surface of a wound even if the honey were diluted more than ten-fold by exudation from the wound.

Cooper R.A. Molan P.C. & Harding K.G. (1999). "Anti-bacterial activity of honey against strains of Staphylococcus aureus from infected wounds." J. R. Soc. Med. 92(6), 283-285.

Abstract. The antibacterial action of honey in infected wounds does not depend wholly on its high osmolarity.

We tested the sensitivity of 58 strains of coagulase-positive Staphylococcus aureus, isolated from infected wounds, to a pasture honey and a manuka honey. There was little variation between the isolates in their sensitivity to honey: minimum inhibitory concentrations were all between 2 and 3% (v/v) for the manuka honey and between 3 and 4% for the pasture honey. Thus, these honeys would prevent growth of S. aureus if diluted by body fluids a further seven-fold to fourteen-fold beyond the point where their osmolarity ceased to be completely inhibitory.

The antibacterial action of the pasture honey relied on release of hydrogen peroxide, which in vivo might be reduced by catalase activity in tissues or blood. The action of manuka honey stems partly from a phytochemical component, so this type of honey might be more effective in vivo. Comparative clinical trials with standardized honeys are needed.

Cooper R.A., Molan P.C., Krishnamoorthy L. & Harding K.G. (2001) "Manuka honey used to heal a recalcitrant surgical wound." Eur J. Clin. Micobiol Infect Dis. 20(10), 758-9.

Cooper R.A. Molan P.C. & Harding K.G. (2002) "The `sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds." J. Applied Microbiol 93(5), 857-63.

Abstract. AIMS: To determine the sensitivity to honey of Gram-positive cocci of clinical significance in wounds and demonstrate that inhibition is not exclusively due to osmotic effects.

METHODS AND RESULTS: Eighteen strains of methicillin-resistant Staphylococcus aureus and seven strains of vancomycin-sensitive enterococci were isolated from infected wounds and 20 strains of vancomycin-resistant enterococci were isolated from hospital environmental surfaces. Using an agar incorporation technique to determine the minimum inhibitory concentration (MIC), their sensitivity to two natural honeys of median levels of antibacterial activity was established and compared with an artificial honey solution. For all of the strains tested, the MIC values against manuka and pasture honey were below 10% (v/v), but concentrations of artificial honey at least three times higher were required to achieve equivalent inhibition in vitro. Comparison of the MIC values of antibiotic-sensitive strains with their respective antibiotic-resistant strains demonstrated no marked differences in their susceptibilities to honey.

CONCLUSIONS: The inhibition of bacteria by honey is not exclusively due to osmolarity. For the Gram-positive cocci tested, antibiotic-sensitive and -resistant strains showed similar sensitivity to honey.

SIGNIFICANCE AND IMPACT OF THE STUDY: A possible role for honey in the treatment of wounds colonized by antibiotic-resistant bacteria is indicated.

Cooper R.A., Halas E. & Molan P.C. (2002) "The efficacy of honey in inhibiting strains of Pseudomonas aeruginosa from infected burns." J. Burn Care Rehab. 23(6), 366-370.

Abstract. Because there is no ideal therapy for burns infected with Pseudomonas aeruginosa there is sufficient need to investigate the efficiency of alternative antipseudomonal interventions.

Honey is an ancient wound remedy for which there is modern evidence of efficacy in the treatment of burn wounds, but limited evidence for the effectiveness of its antibacterial activity against Pseudomonas. We tested the sensitivity of 17 strains of P. aeruginosa isolated from infected burns to two honeys with different types of antibacterial activity, a pasture honey and a manuka honey, both with median levels of activity.

All strains showed similar sensitivity to honey with minimum inhibitory concentrations below 10% (vol/vol) both honeys maintained bactericidal activity when diluted more than 10-fold.

Honey with proven antibacterial activity has the potential to be an effective treatment option for burns infected or at risk of infection with P. aeruginosa.

Dixon B. (2003) "Bacteria can't resist honey." The Lancet Infectious Diseases 3(2), 116.

English H.K., Pack A.R. & Molan PC. (2004). "The effects of manuka honey on plaque & gingivitis: a pilot study." J. Int. Acad. Peridontol. 6(2), 63-67.

Abstract: Research has shown that manuka honey has superior antimicrobial properties that can be used with success in the treatment of wound healing, peptic ulcers and bacterial gastro-enteritis.Studies have already shown that manuka honey with a high antibacterial activity is likely to be non-cariogenic.

The current pilot study investigated whether or not manuka honey with an antibacterial activity rated UMF 15 could be used to reduce dental plaque and clinical levels of gingivitis. A chewable "honey leather" was produced for this trial. Thirty volunteers were randomly allocated to chew or suck either the manuka honey product, or sugarless chewing gum, for 10 minutes, three times a day, after each meal. Plaque and gingival bleeding scores were recorded before and after the 21-day trial period.

Analysis of the results indicated that there were statistically highly significant reductions in the mean plaque scores (0.99 reduced to 0.65; p=0.001), and the percentage of bleeding sites (48% reduced to 17%; p=0.001), in the manuka honey group, with no significant changes in the control group. Conclusion:

These results suggest that there may be a potential therapeutic role for manuka honey confectionery in the treatment of gingivitis and periodontal disease.

French V.M. Cooper R.A. & Molan P.C. (2005) "The anti-bacterial action of honey against coagulase-negative Staphylococci." J. Antimicrob. Biochem. 56(1), 228-231.

Abstract. OBJECTIVES: Development of anti-biotic resistant strains of coagulase-negative Staphylococci has complicated the management of infections associated with the use of invasive medical devices, and innovative treatment and prophylactic options are needed.

Honey is increasingly being used to treat infected wounds, but little is known about its effectiveness against coagulase-negative Staphylococci. The aim of this study was to determine the minimum active dilution of two standardised representative honeys for 18 clinical isolates of coagulase-negative Staphylococci.

METHODS: An agar incorporation technique was used to determine the minimum active dilution, with dilution steps of 1% (v/v) [or steps of 5%v/v of a sugar syrup matching the osmotic effects of honey]. The plates were inoculated with 10 microl. spots of cultures of the isolates.

RESULTS: The honeys were inhibitory at dilutions down to 3.6 +/- 0.7% (v/v) for the pasture honey, 3.4 +/- 0.5% (v/v) for the manuka honey, and 29.9 +/- 1.9 for the sugar syrup.

CONCLUSIONS: Typical honeys are about eight times more potent against coagulase-negative Staphylococci than if bacterial inhibition was due to their osmolarity alone. Therefore, honey applied to the skin at the insertion points of medical devices may have a role in the treatment or prevention of infections by coagulase-negative Staphylococci.

Gethin G. & Cowman S. (2005) "Case series of use of Manuka honey in leg ulceration." Int. Wound. J. 2(1), 10-15.

Abstract. The historical and current literature reports the successful use of honey to manage a diversity of wound aetiologies. However, only in the last 40 years is research on its mode of action and contribution to wound healing being investigated. The challenge of managing chronic non healing wounds generated interest in researching non standard therapies.

The aims of the study were to gain insight into the practical use of Manuka honey in wound management. The objective was to test the feasibility of further rigorous research into the use of honey in the management of chronic wounds. Instrumental case series were used to examine the use of Manuka honey in eight cases of leg ulceration. To collect the necessary data, photographs, acetate tracings, data monitoring and patient comments and observations were used to add greater reliability and validity to the findings. The wounds were dressed weekly with Manuka honey.

The results obtained showed three males and five females with ulceration of different aetiologies were studied. A mean initial wound size for all wounds of 5.62 cm(2) was obtained. At the end of four-week treatment period, the mean size was 2.25 cm(2). Odour was eliminated and pain reduced.

The conclusions drawn were that the use of Manuka honey was associated with a positive wound-healing outcome in these eight cases. Arterial wounds showed minimal improvement only.

Henriques A, Jackson S, Cooper R, Burton N. (2006) "Free radical production and quenching in honeys with wound healing potential." J Antimicrob Chemother. 58(4), 773-7

Abstract. OBJECTIVES: Honey-impregnated wound dressings are now available on drug tariff in the UK, though the modes of action of honeys with antibacterial and wound healing properties are not entirely clear. The action of some but not all of these honeys is linked to the production of hydrogen peroxide on dilution of the honey with wound exudate. The present study investigates both free radical production and the antioxidant potential of some honeys, properties which may have a role to play in wound healing.

METHODS: Free radical production and quenching of three honey types (manuka, antibacterial but non-peroxide-producing; pasture, antibacterial peroxide-producing; commercial heat processed, non-antibacterial) was investigated by electron paramagnetic resonance (EPR) spectroscopy; quenching was also examined using a superoxide quenching assay.

RESULTS: All honeys tested had antioxidant potential, with manuka able to completely quench added radicals within 5 min of spiking. Only the peroxide-producing honey (pasture PS9) was found to form radicals on dilution.

CONCLUSIONS: The ability to modulate production and quenching of free radicals may contribute to the demonstrated ability of some honeys to help in resolving the state of inflammation typifying chronic wounds.

Lusby P.E. Coombes A. & Wilkinson J.M. (2002) "Honey: a potent agent for wound healing?" J. Wound Ostomy Continence Nurs. 29(6), 273-274.

Abstract. Although honey has been used as a traditional remedy for burns and wounds, the potential for its inclusion in mainstream medical care is not well recognized.

Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing. The physicochemical properties (e.g. osmotic effects and pH) of honey also aid in its antibacterial actions.

Research has also indicated that honey may possess anti-inflammatory activity and stimulate immune responses within a wound. The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds. It is also known that honeys derived from particular floral sources in Australia and New Zealand (Leptospermum spp.) have enhanced antibacterial activity, and these honeys have been approved for marketing as therapeutic honeys (Medihoney and Active Manuka honey).

This review outlines what is known about the medical properties of honey and indicates the potential for honey to be incorporated into the management of a large number of wound types.

Lusby P.E., Coombes A.L. & Wilkinson J.M. (2005). "Bacterial activity of different honeys against pathogenic bacteria." Arch. Med. Res. 36(5), 464-467.

Abstract. Renewed interest in honey for various therapeutic purposes including treatment of infected wounds has led to the search for new antibacterial honeys. In this study we have assessed the antibacterial activity of three locally produced honeys and compared them to three commercial therapeutic honeys (including Medihoney and manuka honey).

METHODS: An agar dilution method was used to assess the activity of honeys against 13 bacteria and one yeast. The honeys were tested at five concentrations ranging from 0.1 to 20%.

RESULTS: Twelve of the 13 bacteria were inhibited by all honeys used in this study with only Serratia marcescens and the yeast Candida albicans not inhibited by the honeys. Little or no antibacterial activity was seen at honey concentrations <1%, with minimal inhibition at 5%. No honey was able to produce complete inhibition of bacterial growth. Although Medihoney and manuka had the overall best activity, the locally produced honeys had equivalent inhibitory activity for some, but not all, bacteria.

CONCLUSIONS: Honeys other than those commercially available as antibacterial honeys can have equivalent antibacterial activity. These newly identified antibacterial honeys may prove to be a valuable source of future therapeutic honeys.

Malone M.A., Gatehouse H.S. & Treqidqa E.L. (2001) "Effects of time, temperature & honey on Nosema apis (Microsporidia: Nosematidae), a parasite of the honeybee Apis mellifera (Hymenoptera: Apidae)." J. Invertebrate Pathol 77(4), 258-68.

Abstract. Newly emerged adult bees were fed with Nosema apis spores subjected to various treatments, and their longevity, proportions of bees infected, and spores per bee recorded. Spores lost viability after 1, 3, or 6 months in active manuka or multifloral honey, after 3 days in multifloral honey, and after 21 days in water or sugar syrup at 33 degrees C. Air-dried spores lost viability after 3 or 5 days at 40 degrees, 45 degrees, or 49 degrees C. Increasing numbers of bees became infected with increasing doses of spores, regardless of their subsequent food (active manuka honey, thyme honey, or sugar syrup). Final spore loads were similar among bees receiving the same food, regardless of dose. Bees fed with either honey had lighter infections than those fed with syrup, but this may have been due to reductions in their longevity. Bees fed with manuka honey were significantly shorter lived, whether infected or not.

McGovern D.P., Abbas S.Z., Vivian G. & Dalton H.R. (1999) "Manuka honey against Heliobacter pyroli." J.R. Soc. Med. 92(8), 439.

McIntosh C.D. & Thomson C.E. (2006) "Honey dressing vs. paraffin tulle gras after toe nail surgery." J. Wound Care 15(3), 133-136.

Abstract.

OBJECTIVE: Anecdotal reports suggest that certain honey dressings have a positive effect on wound healing. However there is limited empirical evidence supporting its use. This double-blind randomised controlled trial investigated the effect of a honey dressing on a wound healing following toenail surgery with matrix phenolisation.

METHOD: Participants (n=100) were randomly assigned to receive either an active manuka honey dressing (n=52) or paraffin-impregnated tulle gras (n=48). The primary outcome was time (days) taken for complete re-epithelisation of the nail bed.

RESULTS: Mean healing times were 40.30 days (SD 18.21) for the honey group and 39.98 days (SD 25.42) for the paraffin tulle gras group. Partial avulsion wounds healed statistically significantly faster (p=0.01) with paraffin tulle gras (19.62 days, SD 9.31) than with the honey dressing (31.76 days, SD 18.8) but no significant difference (p=0.21) was found following total avulsion when comparing honey (45.28 days, SD 18.03) with paraffin tull gras dressings (52.03 days, SD 21.3.

CONCLUSION: The results suggest that patients may benefit more from paraffin tulle gras dressings than the honey dressings following partial toenail avulsion. No statistically significant difference was found for healing times after total toenail avulsion., although marginal benefits of the honey dressing on these healing times warrants further investigation.

Moar N.T. (1985) "Pollen analysis of New Zealand honey". New Zealand J of Agric Res. 28(1), 39-70.

Molan P.C., Allen, K. L., Tan, S. T. & Wilkins, A. L. (1989) "Identification of components responsible for the antibacterial activity of Manuka and Viper's Bugloss honeys" paper presented at the Annual Conference of the New Zealand Institute of Chemistry.

Molan P.C. & Allen K.L. (1996) "The effect of gamma-irradiation on the antibacterial activity of honey." J. Pharm. Pharmacol. 48(11), 1206-1209.

Abstract. There is increasing usage of honey as a dressing on infected wounds, burns and ulcers, but there is some concern that there may be a risk of wound botulism from the clostridial spores sometimes found in honey. It is well-established that the antibacterial activity is heat-labile so would be destroyed if honey were sterilized by autoclaving, but the effect of gamma-irradiation on the antibacterial activity of honey is not known.

Therefore an investigation was carried out to assess the effect on the antibacterial activity of honey when the honey was subjected to a commercial sterilization procedure using gamma-irradiation (25 kGy). Two honeys with antibacterial activity due to enzymically-generated hydrogen peroxide and three manuka honeys with non-peroxide antibacterial activity were investigated. The honeys were tested against Staphylococcus aureus in an agar well diffusion assay.

There was no significant change found in either type of antibacterial activity resulting from this form of sterilization of honey, even when the radiation was doubled (to 50 kGy). Testing of honey seeded with spores of Clostridium perfringens and C. tetani (10000 and 1000 spores g-1 of honey, respectively) showed that 25 kGy of gamma-irradiation was sufficient to achieve sterility.

Molan P.C. (1999) "The unique properties of manuka honey" Bee Informed (The Journal of the American Apitherapy Society) 6 (1): 5-6.

Natajaran S, Williamson D., Grey J., Harding K.G. & Cooper R.A. (2001) "Healing of an MRSA-colonized, hydroxyurea-induced leg ulcer with honey." J. Dermatol. Treat. 12(1), 33-36.

Abstract. BACKGROUND: With the ever increasing emergence of antibiotic-resistant pathogens, in particular methicillin-resistant Staphylococcus aureus (MRSA) in leg ulcers, a means of reducing the bacterial bioburden of such ulcers, other than by the use of either topical or systemic antibiotics, is urgently required.

METHODS: We report the case of an immunosuppressed patient who developed a hydroxyurea-induced leg ulcer with subclinical MRSA infection which was subsequently treated with topical application of manuka honey, without cessation of hydroxyurea or cyclosporin.

RESULTS: MRSA was eradicated from the ulcer and rapid healing was successfully achieved.

CONCLUSION: Honey is recognized to have antibacterial properties, and can also promote effective wound healing. A traditional therapy, therefore, appears to have enormous potential in solving new problems.

Patton T., Barret J., Brennan J. & Moran N. (2005). "Use of a spectrophotometric assay for determination of microbial sensitivity to manuka honey." J. Microbiol Methods 64(1), 84-95. Abstract. The antimicrobial activity of manuka honey has been well documented

Molan, 1992a,b,c, (1997) Molan, P.C. (1992). "The antibacterial activity of honey. 1: the nature of the antibacterial activity." Bee World 73 (1) 5-28;

Molan, P.C. (1992). "The antibacterial activity of honey. 2: variation in the potency of the antibacterial activity." Bee World 73(2) 59-76;

Molan, P.C. (1992). "Medicinal uses for honey." Beekeepers Quarterly 26;

Molan, P.C. (1997). "Finding New Zealand honeys with outstanding antibacterial and antifungal activity." New Zealand Beekeeper 4(10) 20-26]. The current bioassays for determining this antimicrobial effect employ a well diffusion (Ahn & Stiles, 1990)

Ahn, C. & Stiles, M.E. (1990). "Antibacterial activity of lactic acid bacteria isolated from vacuum-packed meats." Journal of Applied Bacteriology 69, 302-310], (Weston et al., 1999) [Weston, R.J., Mitchell, K.R., Allen, K.L., 1999. "Antibacterial phenolic components of New Zealand manuka honey." J. Food Chem. 64, 295-301] or disc diffusion (Taormina et al., 2001)

Taormina, P. J., Niemira B.A. & Beuchat L.R. (2001). "Inhibitory activity of honey against food borne pathogens as influenced by the presence of hydrogen peroxide and level of antioxidant power." Int. J. Food Microbiol. 69, 217-225]

Assay using zones of inhibition as indicators of bacterial susceptibility. The development of a 24-h spectrophotometric assay employing 96-well microtiter plates, that is more sensitive and more amenable to statistical analysis than the assays currently employed, was undertaken. This simple and rapid assay permits extensive kinetic studies even in the presence of low honey concentrations, and is capable of detecting inhibitory levels below those recorded for well or disc diffusion assays. In this paper, we compare the assay to both well and disc diffusion assays.

The results we obtained for the spectrophotometric method MIC values show that this method has greater sensitivity than the standard well and disc diffusion assays. In addition, inter- and intra-assay variance for this method was investigated, demonstrating the methods reproducibility and repeatability.

Price S.B. (M.Sc.) "Isolation of antibacterial components from manuka honey." (Thesis, 1991).

Russell K.M., Molan P.C. & Wilkins A.L. (1990) "Identification of some antibacterial constituents of New Zealand manuka honey." J. Agric. Food Chem. 34, 10-13.

Abstract: Some components responsible for the exceptionally high antibacterial activity of manuka honey were isolated by testing fractions of the honey for activity against Staphylococcus aureus. An ethanol-ether extract of the honey was separated by preparative-layer chromatography and the fractions thus obtained were assessed for anti-bacterial effects.

One fairly homogenous fraction was identified as methyl 3,5-dimethoxy-4-hydroxybenzoate (methyl syringate). Combined gas chromatography-mass spectroscopy indicated the presence of this compound in some of the other antibacterial fractions together with methyl 3,4,5-trimethoxybenzoate and 3,4,5-trimethoxybenzoic acid. Authentic specimens of 3,5-dimethoxybenzoic acid (syringic acid) and 3,4,5-trimethoxybenzoic acid and their methyl esters were tested against S. aureus. The acids and to a lesser extent, methyl syringate were found to possess significant anti-bacterial activity.

Sealey D.F (M.Sc.) Chromatographic investigations of the antibacterial activity in manuka honey. (Thesis 1988)



al Somal N., Coley K.E., Molan P.C. & Hancock B.M. (1994) "Susceptibility of Heliobacter pylori to the anti-bacterial activity of manuka honey." J.R. Soc. Med. 87(1), 9-12.

Abstract. Honey is a traditional remedy for dyspepsia, and is still used for this by some medical practitioners although there is no rational basis for its use.

The finding that Helicobacter pylori is probably the causative agent in many cases of dyspepsia has raised the possibility that the therapeutic action of honey may be due to its antibacterial properties. Consequently, the sensitivity of Helicobacter pylori to honey was tested, using isolates from biopsies of gastric ulcers. It was found that all five isolates tested were sensitive to a 20% (v/v) solution of manuka honey in an agar well diffusion assay, but none showed sensitivity to a 40% solution of a honey in which the antibacterial activity was due primarily to its content of hydrogen peroxide.

Assessment of the minimum inhibitory concentration by inclusion of manuka honey in the agar showed that all seven isolates tested had visible growth over the incubation period of 72 h. prevented completely by the presence of 5% (v/v) honey.

Snow M.J. & Manley-Harris M. (2004) "On the nature of non-peroxide antibacterial activity in New Zealand manuka honey." Food Chemistry 84(1), 145-147.

Abstract. Some conclusions, which exist in the literature about the nature of non-peroxide antibacterial activity in manuka honey, have been revisited. The stability of non-peroxide antibacterial activity in manuka honey at basic pH was investigated. At pH 11 antibacterial activity was immediately and irreversibly destroyed.

This indicates that it is not possible to carry out chromatography of honey solutions at elevated pH with the intent to isolate the active fraction. The effect of 10-fold excess of catalase upon the antibacterial assay was examined. No statistical difference in the outcome was observed between the normal amount of catalase and the 10-fold excess.

This indicates that non-peroxide antibacterial activity in manuka honey is not likely to be due to residual hydrogen peroxide.

Snow M.J., Manley-Harris M. & Farr J.M. (2005) "Unique Manuka Factor (UMF) fortified honey" Patent No WO2005120250.

Abstract. The invention relates to UMF amended food stuffs and medicaments. In particular, although not exclusively, the invention relates to UMF fortified honey, methods for the preparation of UMF fortified honey, and methods for the preparation of UMF containing fractions of honey.

Stephen-Haynes J. (2004) "Evaluation of a honey-impregnated tulle dressing in primary care." Br. J. Community Nurs. June 2004 (Suppl), 21-27.

Abstract: Honey has been used for its healing properties for centuries and has been used to dress wounds with favourable results. The emergence of antibiotic resistance and growing interest in "natural" or "complementary" therapies has led to an interest in honey dressings.

Much of the research to date has been related to honey's antibacterial properties. However, the healing properties claimed for honey also include stimulating new tissue growth, moist wound healing, fluid handling and promoting epithelialization.

Until recently, honey had not been developed as a wound management product and was not a certified pharmaceutical device. Activon Tulle is a sterile, non-adherent dressing impregnated with Leptospermum scoparium honey.

The claimed properties of honey dressings would make this a valuable addition to the dressing currently available in the primary care setting. An evaluation was undertaken involving 20 patients with a variety of wounds.

A conclusion is drawn that while further research is needed, medical grade honey does appear to be a valuable addition to the wound management formulary.

Tan S.T., Holland P.T., Wilkins A.L., Molan P.C. (1988) "Extractives from New Zealand honeys. White clover, manuka & manuka unifloral honeys." J. Agric. Food Chem. 36, 453-460.

Abstract. Ether extracts were made from aqueous solutions of manuka (Leptospermum scoparium), kanuka (Leptospermum ericoides), and clover (Trifolium repens) honeys with use of a continuous liquid/liquid extractor. The components of the extracts were methylated before being separated and identified by gas chromatography and mass spectrometry, and also by preparative thin-layer chromatography followed by 'H and 13C NMR analyses.

A total of 61 different compounds were detected, and 56 of these were identified. Their concentrations ranged from 0.1 to 4000 pg/g. Classes of compounds detected included hydrocarbons (C21-C33) and straight-chain-monobasic (C8-C23) dibasic, and aromatic acids.

The concentration of aromatic acids in manuka and kanuka honeys was much higher than in clover honey. These acids were not present in a chloroform extract of manuka flowers, which contained many terpenes, none of which were present in manuka honey.

Compounds reported for the first time in honey include 2-decenedioic, decanedioic, nonanedioic, and octanedioic acids.
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  Manuka Monograph By Tony Burfield


Manuka Monograph by Tony Burfield

(Leptospermum scoparium J.R. & G. Forster).

Botany & Natural Habitat.

Manuka (Leptospermum scoparium J.R. & G. Forster) (Allan 1961) is the most abundant shrub/small tree found in New Zealand, & the only endemic Leptospermum spp. native to New Zealand (Thompson 1989; Porter 2004) out of some seventy-nine known Leptospermum spp. It is an invasive, bushy, usually conical-shaped shrub or tree, which typically grows to 4m., but can reach 6-8m., with stems measuring from 10 -12cm. in diameter (Ward 2000). The branches of the shrub are covered in string bark, which, on breaking, reveals a hard reddish-coloured, or sometimes whitish, wood. The shrub is covered all year in small lanceolate shaped green glossy spiky-ended leaves, and flowers periodically especially May-June, having individual white or sometimes pink hermaphroditic (therefore insect-pollinated) flowers, about 10-12mm. across. The plant shows considerable morphological variation in from, habitat, leaf size & shape, flower & leaf colouration, foliage density etc. (Porter 2004). The branches and leaves are covered in silky white hairs, which release essential oil when rubbed. The shrub is prone to attack by the scale insect Eriococcus orariensis, eradicating it in some areas (Anon 1956), and from the manuka giant scale (a Coelostomidis sp.) which appears as a sooty mold on the foliage.

Manuka shrub is found in scrub-forest all over New Zealand, including the Stewart & Chatham Islands, & in Tasmania, as well as in Australia, growing at elevations ranging from sea level to 1000m. It has also been reported as an alien species on several islands in Hawaii and in New Guinea. Manuka is capable of growing in a variety of acidic and low nutrient soils, from sand dunes to mountainous areas. Ward (2000) points out that manuka shrubs are often confused with the larger & faster growing kanuka plants [Kunzea ericoides (A. Rich) J. Thompson, and the author further provides a number of morphological indicators to distinguish the two species.

The word ‘manuka' comes from the Maori term meaning nervousness or anxiety, and is famously associated with Captain Cook, who's men who made a refreshing tea from manuka leaves, which has to be brewed for a longer period to release the flavour than for conventional tea from Camellia sinensis (many consider manuka tea superior!). The plant parts are used in traditional Maori remedies (Brooker et al. 1987; Riley 1994). The leaves exude a sweet manna which is composed of d-mannitol (Cambie & Seelye 1959) - there is a debate as to the cause of this exudation, whether it be natural or as a result of insect damage (Booker et al. 1991).

Essential oil of Manuka.

As with many species of the Myrtaceae, the essential oil of manuka occurs in schizogenous cavities (oil sacs) on the (underside) of leaf surfaces and the seed capsules, and is obtained in practice by the steam distillation (over 2-6 hours) of the wilted wild harvested terminal leaves and branches which are cut into small pieces before loading into the stills. Sustainable mechanical harvesting of manuka foliage, with re-harvesting after 3-5 years has been described (Anon 2000). Perry et al. (1997) reports the yield of essential oil as ranging from 0.14% to 0.80% dry weight of vegetation, although yields of around 0.5% may be more typical. The volatile oil is extremely variable in composition according to vegetation source (see chemotypes listed below), and variation of certain components has been reported from to maturity, and from natural variability within plants sourced at a single location. The ‘normal' oil presented commercially has been described as an amber coloured liquid; the odour is fresh but rather unpleasant-bitter, clove-terpene like/bitter-herbaceous, resinous, with a hint of fruitiness. The dry-out on a perfumers strip is ambery, slightly scented, and soapy (Burfield 2000). Joulain (1996) previously commented that "the intense characteristic odour of this type of product (referring to tea tree oil from Melaleuca alternifolia) is often a handicap for wider uses, such as body care products. The problem also exists, albeit to a lesser extent, for the essential oil of Leptospermum scoparium (manuka) ..." However the commodity buying public has become familiar & accepting of the earthy aromatic odour of tea tree oil over the years, and these remarks may not now be so appropriate.

Earlier studies on Manuka oil chemistry.

Although analytical work on Manuka oil has been carried out for nearly 100 years initially with the identification of leptospermol (Penfold 1921, Gardner 1924; Gardner 1924a) - later to be renamed leptospermone (Short 1926) - only in the last few years has the chemistry associated with the high variability of the oil started to become clear.. Flynn et al. (1979) identified several mono-& sequiterpenoids in manuka oil by GC-MS & IR spectroscopy. Häberlein & Tschiersch (1994) identified several isoflavones and triterpenoids in a dichloromethane extract of manuka vegetation. The b -triketones exhibit keto-enol tautomerism: one of the possible -enol forms of leptospermone is illustrated below:

[img_assist|nid=272|title=leptospermone|desc=|link=none|align=left|width=300|height=223][img_assist|nid=273|title=leptospermone-enol form|desc=|link=none|align=right|width=300|height=225]


Chemotypes.

Douglas et al. (2001) investigated oils from the foliage of 132 samples from 44 collecting sites on the North Island of New Zealand, and distinguished 5 chemotypes: mono-terpene-rich, sesquiterpene-rich, triketone-enriched, mono-sesquiterpene type and methyl cinnamate types. Previously an unpublished survey carried out by the New Zealand Institute for Crop & Food Research Limited, studied prepared essential oils from manuka leaves gathered from various locations on the S. Island of New Zealand, revealing the presence of four separate chemotypes: monoterpene rich; sesquiterpene rich; enhanced triketones in sesquiterpene rich oils and mixed oils with a balance of monoterpenes and sesquiterpenes (Ward 2000). Later Douglas et al. (2004) conducted a survey analyzing oils from 261 manuka plants across 87 sites in New Zealand and identified 11 chemotypes: a -pinene, sesquiterpene-rich with high myrcene, sesquiterpene-rich with elevated (β-)-caryophyllene and (α-)-humulene; sesquiterpene-rich with an unidentified sesquiterpene hydrocarbon; high geranyl acetate; sesquiterpene-rich with high a -ylangene + a -copaene and elevated triketones; sesquiterpene-rich with no distinctive components; sesquiterpene-rich with high trans-methyl cinnamate; high linalol; and sesquiterpene-rich with elevated elemene and selinene.

Monterpenes

Monoterpenes generally occur at concentrations below 3% in Manuka oils, although high a -pinene chemotypes were identified in the North of the N. Island by Douglas et al. (2004). Other monoterpenes hydrocarbons such as myrcene, and oxygenated monoterpenes such as 1,8-cineole & linalool are also common.


Esters

Low levels of esters such as 3-methyl-3-buten-1-yl benzoate (Christoph 2001) are found in manuka oils, but the occurrence of a trans-methyl cinnamate chemotype (at up to 30% methyl cinnamate) was reported by Douglas et al. (2004) in several S. Island samples. The presence of a cluster of a high geranyl acetate (to 48.6%) chemotype towards the South of the N. Island, was also identified by Douglas et al. (2004).


Sesquiterpenes.

The sesquiterpene content of mauka oils is more substantial and includes those components with cubebene/copaene, elemene, gurjunene/aromadendrene, farnescene/caryophyllene, selinene, calamenene & cadinene types of skeletons (Porter & Wilkins 1998).

Melching et al. (1997) succeeding in isolating & identifying the labile sesquiterpene (-)-(!R,7S,10R)-cadina-3,5-diene, zonarene & (+)-d -amorphene which constitute 5-10% of Manex oil (the trade name of Manuka oil from Te Araroa, East Cape as marketed by Tairawhiti Pharmaceuticals Ltd.).

Beta-triketones.

Sojka (2001) discusses the occurrence of b -triketones in various genera of the Myrtaceae e.g. in Eucalytptus, Leptospermum, Kunzea, Xanthostemon, Backhousia, Melaleuka, Baekea & Callistemon genera, giving examples from the published literature for flavesone, leptospermone & isoleptospermone.

Of the N. Island New Zealand manuka oils, the triketone-enriched East Cape chemotype is rich in the b -triketones flavesone, leptospermone & iso-leptospermone, & has a much lower discernable odour, especially if the oil is fractionated to enhance the concentration of these components. Analytically, the presence of the b -triketones distinguishes manuka oil from Kanuka oil from Kunzea ericoides.


The presence of 3 further minor ketonic compounds in Manuka oil illustrated below was established by Melching (1997) and was confirmed by Porter & Wilkins (1998):







One of these compounds, 2-(1-oxobutyl)-4,4,6,6-tetramethylcyclohexan-1,3,5-trione has previously been named grandiflorone after it was found as a substituent of the Australian essential oil of L. flavescens (Brooker et al. 1963; Hellyer 1968; Brophy et al. 1996).

The East Cape Chemotype of Manuka Oil in More Detail.

Essential oils prepared from manuka vegetation in the N. Island of New Zealand were found to contain from 0.1 to 33.3% (average 5.8%) of the triketones flavescone, isoleptospermone, and leptosepermone (Douglas et al 2001). Later, Douglas et al. (2004) identified b -triketone levels of >20% with only a slight seasonal variation, from surveying 36 plants in the East Cape area, although triketone levels of up to 20% were also found in the Marlborough Sounds area of the S. Island. High triketone plants with triketone levels of >20% only have a limited distribution within the East Cape area, and commercial exploitation of this chemotype is dependent on maximizing foliage production.& regrowth (Douglas et al. 2004)..

Porter (Porter 2004) further comments that under agricultural pressure, wild stands of Manuka are being cleared and that therapeutic lines of the East Cape variety may be lost, although trial plantations have been established. High levels of these compounds are aided by companies involved in East Cape oil production (e.g. Tairawhiti Pharmaceuticals which distills foliage from Te Araroa, East Cape) by prolonging distillation times (4-6 hours), and/or by high-vacuum fractionation of the oil, making oil production a more expensive exercise than, for say, tea-tree oil from Melaleuca alternifolia. Careful analytical monitoring of production batches has to be maintained to ensure product consistency due to the variability of the essential oil from the East Cape vegetation sources. A high β-triketone containing fraction of East Cape manuka oil is commercially available containing over 96% β-triketone ocontent.:

Substituent
%-age
Leptospermone
57.7% to 67.0%

Isoleptospermone
13.0% to 23.0%

Flavesone
13.0% to 23.0%

Table 1. Constituents of high β-triketone fraction of manuka oil.

A mixture of East Cape Manuka oil and Tea tree oil has also been sold commercially as Lema oil (New Zealand Patent 332694 to Coast Biologicals Ltd.). East Cape Manuka oil is also sold with the Manu trademark in a range of concentrations, produced by Manu Nutraceuticals Ltd.

The biosynthetic pathway for the formation of these b -triketones is unknown at present, and Brophy et al. (1999) did not find any b -triketones in Australian L. scoparium samples. Further, Perry et al. (1997) proposes that New Zealand oils from L. scoparium are a different chemotype to the corresponding Australian oils, and that the New Zealand plants are morphologically different from Tasmanian L. scoparium specimens. Further, Porter & Wilkins (1998) advise that kanuka oil is characterized by high levels of a -pinene (>50%) whereas monoterpenes are typically present at low levels ( <3%) in many manuka oils The presence of higher levels of b -triketones has been advised as offering a high level of anti-microbial activity against Gm-positive organisms such as Staphylococcus, Enterococcus & Streptococcus spp., and certain dermatophytic fungi (see below).

Flavonoids.

The flavonoids in a petroleum extract of the aerial parts of manuka, separated on silica gel were characterized by Mayer (1990) who confirmed the identity of seven compounds, four of which were already noted in the literature, and found that a triterpene diol previously identified as betulinol was in fact a mixture of uvaol & betulinol. The new flavonoids were 5-methoxy-7-hydroxy-6,8-dimethylflavone, 5-hydroxy-6-methyl-7-methoxyflavone & 5,7-dimethoxy-6-methylflavone, Further investigations were conducted by Tscheirsch et al. (1992) and Haberlein & Tschiersch (1993) who discovered a further flavanoid, 5,7-dimethoxy-6-methylflavone..




Tannins.

Tannins in Leptospermum scoparium were investigated by Cain (1963).

Triterpene Acids.

Triterpene acids in Leptospermum scoparium were investigated by Corbett & McDowell (1958).

Anti-microbial properties of Manuka oil.

General Remarks.

The manuka oil chemotype, the manuka oil composition and the microbiological testing method employed are some of the major factors with respect to reported anti-microbial activity of manuka oil. Intimate contact between essential oil molecules and micro-organisms, is notoriously difficult to achieve in aqueous media because of the hydrophobicity of essential oils. Various microbiological techniques employed to assess the anti-microbiological activity of manuka oils have included the inhibitory zone technique (Perry et al. 1997), the agar well technique (Lis-Balchin et al. 1996), the broth dilution method (Christoph et al. 2000; Harkenthal et al. 1999) and the broth susceptibility method (Carson & Riley 1994) amongst others. However, various considerations point to test method dependency. For example the effect of any surfactant employed may have a direct bearing on the results. Thus van Zyl et al. (2000) on testing 20 nature identical essential oil constituents remark that in their findings "the relative inactivity of citronellal, (+)-αβ-thujone, p-cymene and 1,8-cineol has been associated with low water solubility & hydrogen bonding capacity, thus limiting their entry into Gm-ive organisms that possess sufficient hydrophobic pathways in the outer membrane (quoting Griffin et al. 1999). Elsewhere Burt (2004) remarks that Gm -ive bacteria are less susceptible to the action of essential oils due to the presence of an lipopolysaccharide coving to the outer membrane to their cell wall which restricts the diffusion of lipophilic compounds.

The anti-microbial properties of mixtures of a high β-triketone fraction of manuka oil with other essential oils have also been investigated e.g. with niaouli or Australian tea tree oil by Christoph et al. (2001). In the latter study good activity was noted against Staphylococcus aureus and Moraxella catarrhalis, with total kill times determined at 240 mins. for both types of admixture, which was superior to that for myrtol, the proprietary product for the treatment of acute and chronic bronchitis and sinusitis. Combinations of manuka and tea tree, calendula and tea extracts & essential oils were tested for potential use as an oral mouthwash against the periodontal pathogens Actinobacillus actinomycetemcomitans, Tanerella forsythensis (Lauten et al. 2005) but the results did not reach statistical significance.

Combinations of the β-triketone fraction of manuka oil and antibiotics have also been investigated against a number of pathogenic organisms (Kim 1999).

Comparative anti-microbiological activity testing.

Christoph et al. (2000) found that Lema oil® came second in kill time performance in a series of oils tested against Staphylococcus aureus (Australian tea-tree oil, cajuput oil, niaouli oil, Lema oil, kanuka oil, manuka & the beta-triketone isolate of manuka oil), where a 2% concentration of oil a complete 6.8 log10 reduction of cell numbers in suspensions within 60 min.

Harkenthal et al. (1999) found that manuka oil had a higher kill activity against Gm +ive bacteria than tea tree oil, with a MIC value of around 0.12%. The authours also found that both manuka and tea tree had a good activity against anti-biotic resistant strains of Staphylococcus aureus, but only a poor activity against Pseudomonas aeruginosa.

Takarada et al (2004) investigated a number of essential oils including manuka, manuka oil, tea tree oil, eucalyptus oil, lavandula oil, and rosmarinus oil against a number of oral pathogens, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sobrinus, finding that that, among the essential oils tested, manuka oil and tea tree oil in particular had strong antibacterial activity against periodontopathic and cariogenic bacteria.

Filoche et al. (2005) tried a number of essential oils including manuka oil, Listerine Coolmint, and menthol & thymol, alone and in combination with chlorhexidine gluconate, against biofilm & planktonic cultures of Streptococcus mutans & Lactobacillus plantarum. Manuka oil showed some activity but less than cinnamon oil.

Virucidal Properties.

Reichking et al. (2005) established the virucial activity of beta-triketone rich manuka oil fractions against the Herpes simplex organisms HSV-1 & HSV-2 in vitro on RC-37 cells (monkey kidney cells) using a plaque reduction assay. Pre-treatment of the viruses with manuka oil for 1 h prior to cell infection showed that significant inhibition could be achieved for both HSV-1 & HSV-2 strains.

Sojka (2005) has investigated the activity of manuka oil and the three beta-triketones against Herpes simplex 1 in various phases of activity, finding that flavesone & manuka oil when in direct contact with the viral plaques were strongly anti-viral.

Dermatophytic organisms.

Action of manuka oil against the dermatophyte Trichophyton mentagrophytes was investigated by Lis-Balchin et al (1996). Tea tree oil was found to have no action, but manuka oil was effective against this organism in this study. Elsewhere, dilutions of 1:1250 have been shown to kill this organism completely over time.

Ethnic Uses of Manuka.

Manuka was renowned for its utilisation as a tea substitute by sailors visiting Aotearoa, hence the name "tea-tree" was born, although manuka is, of course, quite different from tea-tree.

The bark/leaves/sap/seed capsules of manuka have long been used for beverages or medicinal preparations (Best 1905; Brooker et al. 1981). Decoctions of leaves are used as aromatic teas for treating fevers & for treating colds, and as an emetic, purgative & diuretic; oil infusions of manuka leaves have been used against chronic sores (Porter 2004). Pulped manuka seed capsules have been used as wound dressings (Anon 2000). Carr (Carr 2004) presents the ethnic uses of manuka plant parts in tabulated form, largely based on the above noted published information by Brooker et al. (1981).

Young (2001) explores issues in a review which considers the patentability of Maori traditional medicine, citing as a parallel example (that traditional medicine should fall outside the patentable area) the withdrawal of a patent for the medicinal uses of turmeric in India. The above mentioned patent application was contested by Indian scientists who showed the traditional employment of turmeric for this same purpose over hundreds of years. Young cites a little-used morality exclusion in the 1953 New Zealand Patents Act, subsequently retained in a 1994 amendment, which could be employed prevent the patenting of Maori traditional medicine.

Dyeing. A yellow-green dye is obtained from manuka flowers & a greenish-black dye from the flowers, branches & leaves (Grae 1974). Daniels (1997) throws some light on the use of tannin-rich manuka vegetation which is boiled with the leaves of Phormiun tenax and plunged into mud to make a traditional black dye for bark-cloth & baskets by Maori weavers.

Other properties & applications of Manuka oil.

Spasmolytic effect. Lis-Balchin & Hart (1998) & Lis-Balchin et. al. (2000) studying the effects of tea tree, manuka & kanuka oils on guinea-pig ileum, skeletal muscle (chick biventer muscle and the rat phrenic nerve diaphragm) and also rat uterus in vitro, noted a spasmolytic effect in smooth muscle for manuka oil, but it is unclear which precise chemotype of manuka oil was tested. Lis- Balchin & Hart considered a post-synaptic mechanism involving cAMP was implicated in the spasmolytic effect. The authors also warned against the use of all three oils during childbirth based on the in vitro observations on the effects of the essential oils on rat uterus, where they caused a decrease in the force of the spontaneous contractions.

Sedative effect.

Extracts of young leaves & twigs contain methylated & methoxylated flavonoids which interact with agonists at the benzodiazepine GABA-A receptor complex of the CNS (Haberlein & Tshjiersch 1994; Haberlein et al. 1994), similar to the mode of action of axiolytic & anti-convulsant benzodiaxepine drugs. As such, extracts of manuka can be used as part of a treatment regime for subjects withdrawing from benzodiazepine drugs (Ramussen 1997).

Anti-oxidant effect. Lis-Balchin et. al. (2000) noted anti-oxidant effects for manuka oil. Anti-oxidant & free radical quenching abilities of various manuka honeys have been investigated (Henriques et al. 2006).

Effects against proteases. Carr (1998) reported that Manuka can be effective against cysteine proteases implicated in muscle wasting diseases, such as muscular dystrophy, viral replication, tumour invasion etc., building on previous enzyme inhibitory properties shown by manuka (Carr 1991).

Cosmetic uses. Beta-triketone fractions of manuka oil have been incorporated, with other active ingredients, as components of an anti-dandruff shampoo (trademarked Trikenol from the Provital Gp.), based on the alleged fungiostatic properties of the manuka fractions towards Malassezia (:lipophilic yeast) species which proliferate in the scalp sebum.

Manuka has been used in fragrances for toiletries (creams, shampoos, soaps etc.) in New Zealand's domestic market, sometimes in place of Australian tea tree oil. Manuka oil containing soap is used against body odour & acne, and manuka oil is used as an anti-inflammatory against insect bites, sunburn etc. (Porter 2001). Sojka (2005) indicates that the beta-triketones of manuka oil appear stable, presenting an apparent advantage over tea tree oil, the continued use of which in cosmetics has been questioned (see SCCP's controversial Opinion SCCP/0843/04 at http://www.cropwatch.org/sccp_o_018.pdf).

Insecticidal uses. Leptospermone has previously been shown to have some insecticidal properties. A patent has been filed concerning the use of manuka oil against arthropods (Watanabe Keisuke & Sugano Masayo 2003). A number of articles & patents have arisen from the employment of natural triketones & synthetic analogues against micro-organisms (e.g. van Klink et al. 2005).

Leptospermone has also been shown to be herbicidal and cause bleaching of foliage (Knudsen et al. 2000).

General References - see Manuka Biblio.

Extra References for the Manuka Biblio above:

Allan, H. H. (1961). Flora of New Zealand, Vol. 1. Wellington: DSIR.

Best E. (1905) Polynesian Society Journal 13, 213.

Brooker, S. G., Cain, B. F., & Cambie, R. C. (1963). Transactions of the Royal Society of New Zealand, 1, 61.

Brooker, S. G., Cambie, R. C. & Cooper, R. C., New Zealand Medicinal Plants. Heinemann, Auckland, 1981.

Brophy J.J., Goldsack R.J., Forster P.L., Clarkson J.R. & Fookes C.J.R. Journal of Essential Oil Research 8,465.

Burfield T. (2000) Natural Aromatic Materials - Odours & Origins pub. AIA Tampa 2000.

Burt S. (2004) "Essential oils: their antibacterial properties and potential applications in foods - a review." J. Food Microbiol. 94, 223-253.

Cain, B. F. (1963) New. Zeal. J. Sci. 6, 264.

Carr A.C. (1998) "Therapeutic properties of Australian & New Zealand tea trees." New Zealand Pharmacy 18(2) Feb 1998.

Carr A.C (1991) "Inhibitors of the cysteine protease papain from extracts of manuka (Leptospermum scoparium)" BSc Hons Thesis Univ. of Canterbury, Christchurch 41p.

Carson C.F. & Riley T.V. "Susceptibility of Propionibacterium acnes to the essential oil of Melaleuca alternifolia." Letters in Applied Microbiology 19, 24-25 (1994).

Corbett R.E. & McDowell M.A. (1958) J. Chem Soc 3715.

Daniels V. (1997) -see http://www.rbgkew.org.uk/SEB-UK/news0697.htm#{anchor3}

Grae I. (1974) Natures Colours- Dyes from Plants. MacMillan Publ.N.Y.

Hellyer R.O. (1968) Australian J Chem. 21,285.

Knudsen, C.G., Lee, D.L., Michaely, W.J., Chin, H.-L., Nguyen, N.H., Rusay, R.J., Cromartie, T.H., Gray, R., Lake, B.H., Fraser, T.E.M., Cartwright, D. (2000). "Discovery of the triketone class of HPPD inhibiting herbicides and their relationship to naturally occurring b-triketones." In: Narwal, S.S. (Ed.), Allelopathy in Ecological Agriculture and Forestry.

Lis -Balchin M., Deans S. & Hart S. "Bioactivity of New Zealand medicinal plant essential oils." Proc. Intl. Symp. Medicinal & Aromatic Plants eds L.E. Craker, L. Nolan & K. Shedy, Acta Hort. 426, ISHS (1996).

Riley, M. Maori Healing and Herbal. pub. Viking Sevenseas N.Z. Ltd, Paraparaumu, New Zealand, 1994, p. 278.

Short W.I. Journal of the Society of Chemical Industry (1926).

Ward C. (2000) "Kanuka & Manuka" - see http://www.forestandbird.org.nz/publications/magazine/2000/february/Kanu...
Original work URL(s):
  http://www.manukanatural.com/pages/Manuka-Monograph-By-Tony-Burfield.html

Allegedly infringing URLs:

Copyright claim #7:
  Manuka Oil Chemical Composition



Anon (1924) "Essential oil of manuka." Perfume & Essential Oil Record 87,96.

Bick I. R. C., Blackman A. J., Hellyer R. O. & Horn D.H.S. (1965) "The isolation and structure of flavesone." J. Chem. Soc 3690-3693 : 1965.

Briggs L.H., Penfold A.R. & Short W.F. (1938) "Leptospermone Part I." J. Chem Soc. 141(2), 1193-1195.

Briggs L.H., Hassall C.H. & Short W.F. (1945) "Leptospermone Part II." J. Chem Soc. 148, 706-709.

Brophy J. J., Goldsack R. J., Forster P. I., Clarkson, J. R. &
Fookes, C. J. R. (1996) "Mass spectra of some b-triketones from
Australian Myrtaceae." J. Essent. Oil Res. 8, 465-470.

Cambie R.C. & Seelye R.N. (1959) "Note on the identification of manuka manna". N.Z. J. Sci 2(4), 498.

Abstract The colourless, crystalline water-soluble compound found on Leptospermum scoparium & associated with the nymphal form of Scolypopa australis & the larva of Aemona hirta has now been identified as d-mannitol.

Christoph, F.; Kubeczka, K.-H.; Stahl-Biskup, E. (1999) "The composition of commercial manuka oils from New Zealand." J. Essent. Oil Res. 11, 705-710.

Corbett R.E. & McDowall M.A. (1958) J. Chem Soc. 7315.

Douglas M.H., van Klink J.W., Bruce M., Smallfield B.M., Perry N.B.,
Anderson R.E., Johnstone P. & Weavers R.T. (2004) "Essential oils
from New Zealand manuka: triketone and other chemotypes of Leptospermum scoparium." Phytochemistry 65(9) May 2004, pp1255-1264.

Abstract: The triketone chemotype of manuka, Leptospermum scoparium
(Myrtaceae), is commercially important because of its antimicrobial
activity. Oils from 36 individual plants on the East Cape of New
Zealand all showed similar high triketone contents (>20% total
triketones) with little seasonal variation.

Analyses of oils from 261 individual manuka plants collected from 87
sites throughout New Zealand showed that the high triketone chemotype
was localised on the East Cape, although oils with triketone levels up
to 20% were found in the Marlborough Sounds area of the South Island.

Cluster analysis revealed other chemotypes localised on other areas.
Ten further chemotypes are described: a-pinene; sesquiterpene-rich with
high myrcene; sesquiterpene-rich with elevated caryophyllene and
humulene; sesquiterpene-rich with an unidentified sesquiterpene
hydrocarbon; high geranyl acetate; sesquiterpene-rich with high
g-ylangene + a-copaene and elevated triketones; sesquiterpene-rich with
no distinctive components; sesquiterpene-rich with high trans-methyl
cinnamate; high linalol; and sesquiterpene-rich with elevated elemene
and selinene.

Some of the chemotypes contained aroma compounds at relatively high
levels, with a geranyl acetate-rich oil being most notable. Possible
origins for this complex array of chemotypes are proposed.

Douglas M., Anderson J., van Klink J., Perry N. & Smallfield B.
(2001) "Defining the North Island manuka chemotype resources - a survey
report." Crop & Food Research Report No. 447 New Zealand Institute for Crop & Food Research Limited.

Flynn T.M., Lassak E.V., & Smyth M.P. (1979). "The volatile leaf oils of three species of Leptospermum." Phytochemistry 18, 2030-2031.

Gardner R. (1924). "The essential oil of Manuka (Leptospermum scoparium)". J. Soc. Chem. Ind. 43, 34-35.

Gardner R. (1924). "The essential oil of Manuka (Leptospermum scoparium)". J. Soc. Chem. Ind. 44, 528-530.

Gardner R. (1924). "The essential oil of Manuka (Leptospermum scoparium)". J. Soc. Chem. Ind. 45, 96-98.

Haberlein, H. & K. P. Tschiersch (1998). "On the occurrence of methylated and methoxylated flavonoids in Leptospermum scoparium." Biochemical Systematics and Ecology 26(1), 97-103.

Abstract. Samples of Leptospermum scoparium,
collected from climatically and geologically different locations, were
examined for their external leaf flavonoids. HPLC fingerprint analyses
of dichloromethane extracts revealed different compositions and amounts
of methylated and methoxylated flavonoids.

In the area of Auckland, Coromandel, Whangaruru North, and Rawhiti
plants have been found which possess high amounts of pharmacologically
active 5,7-dimethoxyflavone, 5-hydroxy-7-methoxy-6-methylflavone, and
5-hydroxy-7-methoxy-6,8-dimethylflavan-3-one.

Haberlein, H. & K. P. Tschiersch (1994). "2,5-Dihydroxy-7-methoxy-6,8-dimethylflavan-3-one a novel flavonoid from Leptospermum scoparium: In vitro affinity to the benzodiazepine binding site of the GABA-A receptor-chloride channel complex." Pharmazie 49(11), 860.

Haberlein, H., K. P. Tschiersch, et al. (1994). "Flavonoids from Leptospermum scoparium
with affinity to the benzodiazepine receptor characterized by structure
activity relationships and in vivo studies of a plant extract." Pharmazie 49(12), 912-922.

Abstract. The New Zealand Myrtacea Leptospermum scoparium
Forst. contains lipophilic flavonoids which interact specifically with
benzodiazepine receptors. For an in depth characterization of their
binding behaviour, structure activity relationships were delineated
which are in accord with results obtained by quantum-chemical and
spectroscopic methods.

Inhibition experiments have been performed by a radio receptor assay
with [3H]flunitrazepam and IC50-values of 2.1 microM for
5,7-dimethoxyflavone (1), 45 microM for 5,7-dimethoxy-6-methylflavone
(2), 3.3 microM for 5-hydroxy-7-methoxy-6-methylflavone (3) and 40
microM for 5-hydroxy-7-methoxy-6,8-dimethylflavone (4) have been
measured. Flavanones 5 to 8, however, at concentrations < or = 0.1
mM, did not show a 50% inhibition of the binding radiolignand.

The agonistic profile of the flavones was determined indirectly by
TBPS-shift experiments which revealed a negative cooperation with the
TBPS/picrotoxinin-binding site. To characterize the biologically active
conformations, energy minima were calculated using the semiempirical
method AM1.

The steric arrangement of the substituents for all global minima
calculated were in accord with homonuclear NOE-experiments. A
correlation of the geometry of the lowest energy conformers with
corresponding IC50-values reveals an increase of the affinity towards
the benzodiazepine receptor, when the substituents at the flavones are
coplanar to the aromatic system and R3 represents a sterically
demanding methylgroup. Analyses of the global minima of
5,7-Dimethoxyflavone and diazepam showed one conformer each, in which
the methoxy substituent in R3 and the N-methyl on the one hand and the
corresponding carbonyl oxygens as well as the unsubstituted phenyl
rings on the other were nearly superimposable.

The flavanones lacking the double bond between C-2 and C-3 have
angular structures, whereby the loss of affinity to the receptor can be
explained. >From the locomotion study with rats, an in vivo sedating, possibly even anxiolytic effect of the dry extract of the tincture prepared from Leptospermum scoparium
by use of 70% ethanol, could be concluded. At doses of 50 mg and 250 mg
of the dry extract per kg of body weight, an unequivocal but not linear
dose-activity relationship in respect to the moving activities of the
animals was determined.

Upon an application of 500 mg of this extract per kg body weight,
by contrast, only a negligible reduction of the moving activity was
found in relation to a control group. We suppose that at higher doses,
activating compounds of the extract come to the fore pharmacologically
neutralizing the primarily sedating effect.

Haberlein, H. & K. P. Tschiersch (1994). "Triterpenoids and flavonoids from Leptospermum scoparium." Phytochemistry Oxford 35(3), 765-768.

Abstract. An investigation of the dichloromethane extract of Leptospermum scoparium
afforded seven 3-substituted triterpenoid acids, four of which were
novel, and eight methylated flavonoids including one new flavone.

The new compounds were identified by their spectroscopic data as 3β-O-trans-ferulyl-2α-hydroxy-urs-12-en-28-oic acid, 3β-O-cis-ferulyl-2α-hydroxy-urs-12-en-28-oic acid, 2α-O-trans-ferulyl-3β-hydroxy-urs-12-en-28-oic acid, 3β-O-cis-coumaroyl-2α-hydroxy-urs-12-en-28-oic acid and 5,7-dimethoxy-6-methylflavone.

Hellyer R.O. (1968) "The occurrence of beta-triketones in the steam volatile oils of some myrtaceous Australian plants." Australian Journal of Chemistry 21, 2825-2828.

Joulain D. (1996). "Investigating new oils: rationale, results, limitations." Perfumer & Flavourist 21(2),1.

van Klink J.W., Brophy J.J. Perry N.B & Weavers R.T. (1999) "b-Triketones from the Myrtaceae: Isoleptospermone from Leptospermum scoparium & papuanone from Corymbia dallachiana." J. Nat. Products 62, 487-489.

Abstract. Naturally occurring beta-triketones, isoleptospermone
[3,5-hydroxy-4-(2-methyl-1-oxopentyl)-2,2,6,6-tetramethyl-4-cyclohexene-1,3-dione)
from Leptospermum scoparium] and papuanone [6,5-hydroxy-4-(1-oxohexyl)-2,2,6,6-tetramethyl-4-cyclohexene-1,3-dione from Corymbia dallachiana] have been synthesised.

Full spectra data are reported for the first time. The 13C NMR spectra
of 3,6 and the other triketones flavesone (2), leptospermone (4) and
grandiflorone (5) found in Myrtaceous plants are fully assigned.



Maddocks-Jennings W., Wilkinson J.M., Shillington D. & Cavanagh
H. (2005). " A fresh look at manuka and kanuka essential oils from New
Zealand." International Journal of Aromatherapy 15(3), 141-146.

Summary: Essential oil is obtained from manuka, Leptospermum scoparium and kanuka, Kunzea ericoides,
which are indigenous plants to New Zealand. The oil from these plants
has been commercially available to aromatherapists for more than a
decade. In this time, attention has been given to the antiseptic and
antimicrobial actions of the oils.

Of most interest to researchers and aromatherapists is the presence of
beta-triketones, present in the manuka oil. These triketones are
believed to significantly contribute to the antimicrobial action.

More recently, it has emerged that there are significant geographical
variations affecting the composition of these oils. Whilst a full
understanding of the therapeutic implications is some way off, it is
important for aromatherapists to appreciate that these differences
exist and the oils selected may match the intended therapeutic purpose.



Mayer, R. (1996). "Three lupane derivatives from Leptospermum scoparium." Archiv der Pharmazie Weinheim 329(10), 447-450.

Abstract. An investigation of L. scoparium afforded three new flavonoids. A previously mentioned triterpene diol appeared as a mixture of uvaol and betulinol.

Mayer, R. (1993). "A b-hydroxychalcone from Leptospermum scoparium." Planta Medica 59(3), 269-271.

Mayer, R. (1990). "Flavonoids from Leptospermum scoparium." Phytochemistry 29(4), 1340-1342.

Melching S., Bülow N., Wihstutz K., Jung S. & König W.A. (1998?)
"Natural occurrence of both enantiomers of cadina-3,5-diene and &
d-amorphene." Phytochemistry 44, 1291-1296.

Abstract: The labile sesquiterpene hydrocarbon (-)-(1R,7S,10R)-cadina-3,5-diene was isolated from manuka oil (Leptospermum scoparium) by preparative gas chromatography, while its enantiomer is present in a chemotype of the liverwort Conocephalum conicum collected in southern Germany.

The structure and absolute configuration was derived by NMR
investigations, enantioselective gas chromatography and by conversion
into a series of products of known stereochemistry by acid catalysed
rearrangement, e.g. (-)-(7S,10R)-trans-calamenene,
(-)-(7S,10R)-cadina-1(6),4,diene,
(-)-(1R,7S,10R)-bicyclosesquiphellandrene and (-)-(1R,10R)-zonarene.
In addition, (+)-d-amorphene was identified as a constituent of L. scoparium, whilst (-)-d-amorphene is present in vetiver oil.

Both enantiomers of this sesquiterpene, which has not been described as
a natural product so far, were prepared by rearrangement of an
enantiomeric mixture of germacrene D isolated from Solidago canadensis.

Ogura M., Cordell G.A. & Farnsworth (1977) Phytochemistry 16, 286.



Perry, N. B., Brennan N.J., van Klinck J.W., Harris W., Douglas
M.H., McGimpsey J.A., Smallfield B.M. & Anderson R.E. (1997).
"Essential oils from New Zealand manuka and kanuka: Chemotaxonomy of Leptospermum." Phytochemistry 44(8), 1485-1494.

Abstract. A standardized analytical GC method has been used to analyse essential oils from selected Australian and New Zealand Kunzea species, grown from seed at a single site.

The distillation yields and analyses are reported for oils from 26 populations of K. ericoides (kanuka) and from single populations of each of K. flavescens, K. pauciflora, K. sinclairii and x Kunzspermum hirakimata (a Kunzea x Leptospermum cross).

Principal components analyses of 37 GC peaks in these oils were used to distinguish compositional patterns. Oils from K. flavescens, K. pauciflora and x Kunzspermum hirakimata had chemical compositions distinct from K. sinclairii and K. ericoides.

Oils front New Zealand K. ericoides were mainly α-pinene (mean 68%), but some oils had high p-cymene contents, particularly oils from one Marlborough provenance (mean 31%). A wild population of K. ericoides var. linearis gave oils with similar composition to other K. ericoides. Two K. ericoides oils showed weak antifungal activity.



Porter, N. G., Smale P. E., Nelson M.E., Hay A.J., van Klink J.W.
& Dean C.M. (1998). "Variability in essential oil chemistry and
plant morphology within a Leptospermum scoparium population." New Zealand Journal of Botany 36(1), 125-133.

Abstract. Essential oil composition and plant morphology were
observed over four years in individual plants raised from seed of a
wild population of Leptospermum scoparium (Myrtaceae) collected
at a single site in New Zealand. Principal component analyses of data
from young and mature plants showed no significant grouping of plants
on the basis of oil composition, but identified differences between the
essential oil components contributing most to variation in oil
composition in both young and mature plants.

The dominant variables were six sesquiterpene components in young
plants, and three monoterpenes and two sesquiterpenes in mature plants.
Levels of these components differed significantly at the population
level between young and mature plants and also within and between
seasons. Levels of all these components varied markedly within and
between individual plants at all sample times. The habit, leaf size and
density, and stem and foliage colour also varied markedly between
individual plants.

The variation observed indicates the need for more extensive sampling
and statistical analysis over more than one growing season if
sufficiently reliable data on essential oil compositions in individual
plants or populations are to be obtained for chemotaxonomic or plant
selection purposes.



Porter N.G. & Wilkins A.L. (1999) "Chemical, physical and antimicrobial properties of essential oils of Leptospermum scoparium and Kunzea ericoides." Phytochemistry Oxford 50(3), 407-415.

Abstract: The major components of commercial New Zealand essential oils of Leptospermum scoparium (manuka) and Kunzea ericoides (kanuka) are identified.

In the manuka oil, monoterpenes are present at low levels (³3%).
Sesquiterpene hydrocarbons are predominant (³60%) and include groups
possessing cubebene/copaene, elemene, gurjunene/aromadendrene,
farnesene/caryophyllene, selinene, calamenene and cadinene skeletons.

Oxygenated sesquiterpenes and triketones are present (³30%). The
antimicrobial activity of the manuka oil was associated with a fraction
containing three major and three trace triketones, two of the latter
were previously unreported.

Kanuka oil was characterized by high levels of a-pinene (>50%) and
lower levels ( <10%) of viridiflorol and viridiflorene. GC-MS and
GC-FID detector responses to the same components were noticeably
different for some major components, including the triketones.

Non-commercial manuka oils from different sites differed widely in
composition and could be separated into four groups by the presence and
levels of distinctive components. The density and refractive index of
manuka and kanuka oils were closely correlated with the total
sesquiterpene levels.

The density of the commercial manuka oil was closely correlated with
the level of the triketones. Simple density measurements enabled
discrimination between the commercial oil and oils from other sites,
and prediction of antimicrobial activity.

Short W.F. (1926) "The essential oil of Manuka (Leptospermum scoparium)." J. Soc. Chem. Ind. 45, 96-98.

Tschiersch, K.-P. Dissertationes botanicae, Vol. 241. Leptospermum scoparium J.
R. & G. Forst.: "Isolation, structural explanation, and analysis of
flavonoids and resin esters with in vitro affinity to GABAA receptor
chloride channel complex." Gebr. Bornträger Verlagsbuchhandlung, Stuttgart, 1995.

Wilkins L. (1997). "Chemical & compositional analyses of New Zealand manuka & kanuka oils." Proceedings of Pacific Oils 2000 Conference Nov 1997, Auckland.
Original work URL(s):
  http://www.manukanatural.com/pages/Manuka-Oil-Chemical-Composition.html

Allegedly infringing URLs:
  0.   http://www.manuka-products.co.nz/index.php?route=cms/article&path=4&article_id=3

Copyright claim #8:
  Manuka Oil Related Articles


Balunas M. & Kinghorn A.D. (2005) "Drug discovery from medicinal plants." Life Sciences 78(5), 431-441.

Davis C. & Ward W. (2003) "Control of Chalkbrood disease with natural products". RIRDC Publication 03/107 Dec 2003.

Executive Summary: Chalkbrood is a highly contagious disease of the honeybee Apis mellifera caused by the heterothallic fungus Ascosphaera apis. It was first identified in Queensland in 1993, and, since that time, the disease has spread throughout Australia. Although not usually fatal, the disease causes reduced honey production. The effects of chalkbrood can be controlled by improved management techniques such as strengthening colonies with bees or hatching brood and enlarging colony entrances to aid ventilation.

While chalkbrood infections have been related to stress factors, sensible management practices can reduce the numbers of spores of Ascosphaera apis in infected hives and hive equipment. Some hives appear to be more resistant to chalkbrood disease than others due to the ability of their adult bees to uncap and remove affected brood. The disease appears to be most prevalent in the spring when the brood area is increasing.

The presence of chalkbrood in a colony can prevent normal colony growth and can seriously affect the honey production of the hive. While a broad range of chemicals have been used either in hives or in the laboratory to control chalkbrood, no chemicals for the treatment of chalkbrood have been registered for use in Australia and no specific strategy has been universally adopted or accepted by beekeepers around the world. Chalkbrood-resistant bees have been shown to exist naturally in Australia, but the large-scale production of such bees either overseas or in Australia has been slow.

The thermal destruction (time/temperature) parameters have been determined for Ascosphaera apis in honey and the sensitivity of Ascosphaera apis to γ-irradiation using Cobalt 60 has been estimated. Such treatments of honey or other bee products can reduce the spread of the disease. There has been an increased interest in the investigation of alternative controls strategies. A compound for control of chalkbrood should have the following three characteristics.

First, it must completely control the disease, or more realistically, keep it below the natural infection rate. Second, the control must be convenient to use, since practices such as applying chemicals and cleaning the bottom boards of colonies every week are not practical for commercial beekeepers with large numbers of colonies. Third, the control must not be more expensive than the natural loss due to the disease.

This project has investigated the antifungal efficacy of over 50 natural products and found that a number of essential oils were particularly efficacious at controlling the in vitro growth of Ascosphaera apis. Of these, citral-containing oils were the most active, with growth inhibition at 250 ppm. These findings need to be progressed to field studies to evaluate product efficacy in the hive and to determine whether residues are a problem with this form of disease control.

The most active antifungal test agents in this study were Nepalese Lemon Grass oil, Lemon Scented Eucalyptus (Eucalyptus citrodora) oil, Lemon Scented Tea Tree (Leptospermum petersonii) oil and a particular fraction of a New Zealand Manuka (Leptospermum scoparium) oil.

All of these agents presented with a Minimal Fungicidal Concentration against Ascosphaera apis of 250 ppm. Citral is the major component of the former three oils while the active chemical in the New Zealand Manuka (Leptospermum) oil is a unique terpenoid agent (leptospermone).

Interestingly, a number of other oils which should have contained significant levels of citral (East Indian Lemon Grass oil, cold-pressed Lemon oil, Natural citral and lemon essential oil) returned negative MFC scores at 1000 ppm or greater. Several other oils exhibited moderate antifungal activity (active at 500 ppm) against Ascosphaera apis (Citricidal, several Tea Tree oils, a number of other New Zealand Leptospermum oils, a ginger oil and a lavender oil).

The remaining essential oils were shown to be ineffectual against Ascosphaera apis in this in vitro test system. This project has also proposed a field test system to assess the efficacy of the most active antifungal agents identified in the in vitro assay system presented in this report.

There are few reports in the literature of field trials of natural products against bee diseases, and even fewer investigating the efficacy of natural products against the causative agent of chalkbrood in an apiary system.

Filoche S.K., Soma K. & Sissons S.H. (2005) "Anti-microbial effects of essential oils in combination with chlorhexidine digluconate." Oral Microbiol Immunol 20(4), 221-225.
Abstract. The aim of the present study was to compare antimicrobial effects of essential oils alone and in combination with chlorhexidine digluconate against planktonic and biofilm cultures of Streptococcus mutans and Lactobacillus plantarum.

The essential oils included cinnamon, tea-tree (Melaleuca alternifola), manuka (Leptospermum scoparium), Leptospermum morrisonii, arnica, eucalyptus, grapefruit, the essential oil mouthrinse Cool Mint Listerine and two of its components, menthol and thymol.

Cinnamon exhibited the greatest antimicrobial potency (1.25-2.5 mg/ml). Manuka, L. morrisonii, tea-tree oils, and thymol also showed antimicrobial potency but to a lesser extent. The combination effect of the essential oil-chlorhexidine was greater against biofilm cultures of both S. mutans and L. plantarum than against planktonic cultures.

The amount of chlorhexidine required to achieve an equivalent growth inhibition against the biofilm cultures was reduced 4-10-fold in combination with cinnamon, manuka, L. morrisonii, thymol, and Listerine.

We conclude that there may be a role for essential oils in the development of novel anticaries treatments.

van Klink J.W., Larsen L., Perry N.B., Weavers R.T., Cook G.M., Bremer P.J., MacdKenzie A.D. & Kirikae T. (2005) "Triketones active against antibiotic-resistant bacteria: Synthesis, structure-activity relationships, and mode of action." Bioorganic & Medicinal Chemistry 13(24), 6651-6662 .
Abstract. A series of acylated phloroglucinols and triketones was synthesized and tested for activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE) and multi-drug-resistant Mycobacterium tuberculosis (MDR-TB). A tetra-methylated triketone with a C12 side chain was the most active compound (MIC of around 1.0 μg/ml against MRSA) and was shown to stimulate oxygen consumption by resting cell suspensions, suggesting that the primary target was the cytoplasmic membrane.

Meazza G., Scheffler B.E., Tellez M.R., Rimando A.M., Romagni J.G., Duke S.O., Nanayakkara D., Khan I.A., Abourshed A. & Dayan F. E. (2002). "The inhibitory activity of natural products on plant p-hydroxyphenylpyruvate dioxygenase." Phytochemistry 60(3), 281-288.
Abstract. The inhibitory activity of 34 natural products of various structural classes on hydroxyphenylpyruvate dioxygenase (HPPD), the target site for triketone herbicides, and the mode of interaction of selected natural products were investigated. Recombinant HPPD from Arabidopsis is sensitive to several classes of natural compounds including, in decreasing order of sensitivity, triketones, benzoquinones, naphthoquinones and anthraquinones.

The triketone natural products acted as competitive tight-binding inhibitors, whereas the benzoquinones and naphthoquinones did not appear to bind tightly to HPPD. While these natural products may not have optimal structural features required for in vivo herbicidal activity, the differences in their kinetic behaviour suggest that novel classes of HPPD inhibitors may be developed based on their structural backbones.

Rammussen P.L. (1997) "Phytotherapy in the treatment of benzodiapine withdrawal." Eur. J. Herb. Med. 3(1), 11-21.

Schmolz E., Doebner R., Auste R., Daum R., Welge G. & Lamprecht I. (1999) "Bioenergetic investigations on tea-tree and related essential oils." Thermochimica Acta 337(1-2), 71-81.
Abstract. Direct and indirect calorimetry were used to determine the metabolic rates of the bacterium Escherichia coli and the baker's yeast Saccharomyces cerevisiae under the influence of five tea-tree oils and some of their constituents.

Bacteriostatic and bactericidal as well as fungicidal effects were observed, dose-effect curves established, and the kinetics of the inactivation evaluated. Experiments showed that subpopulations of the E. coli suspensions were less sensitive against these essential oils than the whole population and were able to continue to metabolize and to grow.

Spooner-Hart R.N. & Basta A.H. (2004). "Methods and compositions for controlling pests." Patent No EP1392119. Status: request for examination has been made.
Abstract: Not available. Abstract for corresponding patent WO02089587: The present invention is directed to pest-controlling compositions comprising as active ingredients one or more ss-diones, particularly ss-diketones and ss-triketones, and to the use of these compositions inter alia for preventing, eradicating, destroying, repelling or mitigating harmful, annoying or undesired pests including insects, arachnids, helminths, molluscs, protozoa and viruses.

The present invention is further directed to processes of preparing ss-diones by de novo synthesis or from natural sources such as volatile oil-bearing plants from families including Alliaceae, Apiaceae, Asteraceae, Cannabinaceae, Lamiaceae, Pteridaceae, Myrtaceae, Myoporaceae, Proteaceae, Rutaceae and Zingiberaceae

Dissertation.

Chistoph F. (2001) "Chemische zusammensetzung und antimikrobielle eigenschaften der ätherischen öle von Leptospermum scoparium J. R. et G. Forst. und anderer Teebaumöle der Gattungen Kunzea, Leptospermum und Melaleuca unter besonderer Berücksichtigung von Handelsölen" Univ. Hamburg 2001 - see http://www.sub.uni-hamburg.de/opus/volltexte/2001/448/pdf/Dissertation.p...

Sojka C. (2005) "Eigeschaften und antimikrobielle Wirksamkeit von β-Triketonen in ätherischen Ölen der Myrtaceae." Univ. Hamburg 2001. See - http://www.chemie.uni-hamburg.de/bibliothek/2005/DissertationSojka.pdf

Miscellaneous Reports.

Siew D. (2006) "Manuka knocks 'em dead in Singapore." see http://www.irl.cri.nz/newsandevents/innovate/manuka-knocks-dead-singapor...

Monographs.

Anon (2000) "Essential oil production from manuka & kanuka" Crop & Food Research [Broadsheet] No 116 July 2000. New Zealand Institute for Food & Crop Research.

Porter N. (2001) "Manuka: the good oil from New Zealand." Herbalgram 53, 26-30.

Porter N. (2004) "Manuka Oil - New Zealand's answer to Australian tea tree oil." Herbclip 030646-260 .

Oral Hygiene Studies.

Lauten J.D., Boyd L., Hanson M.B., Lille D., Gullion C. & Madden T.E. (2005) "A clinical Study: Melaleuca, Manuka, Calendula & Green Tea Mouth Rinse." Phytotherapy Research 19(11), 951-957.
Abstract. A novel mouthrinse (IND 61,164) containing essential oils and extracts from four plant species (Melaleuca alternifolia, Leptospermum scoparium, Calendula officinalis & Camellia sinensis) were tested.

This study aimed to evaluate safety, palatability, & preliminary efficiency of the rinse. Fifteen subjects completed the Phase 1 safety study. Seventeen subjects completed the Phase II randomised placebo-controlled study. Plaque was collected, gingival & plaque indices were recorded (baseline, 6 weeks & 12 weeks).

The relative abundance of two periodontal pathogens (Actinobacillus actinomycetemcomitans, Tanerella forsythensis) was determined using digoxigen-labelled DNA-probes. ANCOVA was used at the p=0.05 level of significance. Two subjects reported a minor adverse event. One subject withdrew from the study. Several subjects objected to the taste of the test rinse but continued treatment.

Differences between gingival index, plaque index, or relative abundance of either bacterial species did not reach statistical significance when comparing nine placebo subjects with eight test rinse subjects.

Subjects exposed to the test rinse experienced no abnormal oral lesions, altered vital signs, changes in liver, kidney or bone marrow functions. Larger scale studies would be necessary to determine the efficacy & oral health benefits of the test rinse.

Patents - Manuka Biocidal Properties Related.

Corthesy-Theulaz I., Bergonzelli G., Audrin A. Marion J-L. & Aeschbach R. (2004) "Use of essential oils for combating GI tract infection by heliobacter-like organisms" Patent No NZ523838.
Abstract: A nutritional composition which comprised an essential oil selected from the group which consists of carrot seeds, cinnamon bark, clove, cumin, eucalyptus, grapefruit, lemon grass guatemala, manuka oil, oregano (vulgaris) sage, savory, tarragon, thyme, a combination of two or more thereof and/or a compound isolated from one of the essential oils wherein the compound is selected from the group which consists of alpha-pinene, beta-pinene, carvacrol, citral, citronellal, estragole, eugenol, farnesol, geranul acetate, geraniol, isoeugenol, limonene, linalool, nerol, perilla aldehyde, thymol, trans-2-hexenal or a combination of two or more thereof for use in the prevention or treatment of infection by a gastric Helicobacter-like organism; a method of producing the composition; and a method of prevention or treatment of infection by a gastric Helicobacter-like organism in a companion animal which comprises the step of consuming or administering a functional food product or medicament which comprises an effective amount of the composition.

Perry N.B., van Klink J.W., Larsen L. & Weavers R.T. (2003) "Antibacterial Compounds." Patent WO03051806.
Abstract. There is an on-going need for new antibiotics which may be effective against bacteria that are otherwise difficult to control.

The present invention therefore relates to new anti-bacterial triketone compounds of Formula (1) or salts, metal complexes or tautomeric forms of these compounds. The compounds have potential as novel antibiotics.

Thus, the invention also relates to methods of treatment or prevention of bacterial infections using the compounds, and to compositions containing them.

Watanabe Keisuke & Sugano Masayo (2003) "Agent for controlling harmful arthropod containing oil of Leptospermum scoparium." Patent No: JP2003055123 dated 26-02-2003.
Abstract: PROBLEM TO BE SOLVED: To obtain a new agent for controlling a harmful arthropod derived from a natural product because the new agent derived from the natural product is required in a field of the agent for controlling the harmful arthropod in connection with the enhancement of health consciousness and naturalism consciousness of human beings in recent years.
SOLUTION: This agent for controlling the harmful arthropod contains an oil of Leptospermum scoparium which is an essential oil component of the Leptospermum scoparium which is a plant naturally growing in New Zealand.
Original work URL(s):
  http://www.manukanatural.com/pages/Manuka-Oil-Related-Articles.html

Allegedly infringing URLs:
  0.   http://www.manuka-products.co.nz/index.php?route=cms/article&path=4&article_id=7

Copyright claim #9:
  Dermatitis


Cause

The cause of Seborrheic dermatitis is not fully understood, but it may be related to hormones. It is more commonly a male problem which suggests that androgen hormones play a role in its presence.

Dandruff occurs when the scalp sheds its outer layer in clumps rather than in fine particles which are not normally visible. Dandruff is a result of excessively oily skin rather than dry skin. It might also be caused by a fungus, called malassezia, normally present on the skin in small numbers, but in cases of Seborrheic dermatitis, can be present in much larger concentrations.

Symptoms

Seborrheic dermatitis is an inflammatory disorder affecting areas of the head and body where sebaceous glands are most prominent that can vary from mild dandruff to dense flakey and greasy scale. It is common in adolescents and adults in the form of dandruff, while in babies, it is known as cradle cap. In more serious cases it can also affect the skin on other parts of the body, such as the face and chest, and the creases of the arms, legs and groin, and manifest itself as dense flakey and greasy scale.

Chronic dermatitis refers to a longstanding irritable area. It is often darker than the surrounding skin, thickened (lichenified) and much scratched.

Psychological stresses can provoke or aggravate dermatitis, presumably by suppressing normal immune mechanisms.

Treatments

Conventional treatment of Seborrheic dermatitis in the hair usually involves the use of shampoos containing anti-fungal agents salicylic acid, selenium sulfide or pyrithione zinc. When other areas of the body are affected, steroid creams are often prescribed.

Alternative Natural Treatments

Manuka oil and Manuka UMF® honey provide an effective natural alternative to synthetic drug formulations, in mild cases of Dandruff, a shampoo containing Manuka oil will be a useful natural alternative to shampoos containing salicylic acid, selenium sulfide or pyrithione zinc, and as it is a completely natural product, is safe for infants. An additional advantage of using Manuka shampoo is its ability to rid the hair of head lice, a common problem for school age children.

In more severe cases, diluted Manuka Essential oil and creams containing Manuka oil will be very helpful as will the use of Manuka soap.

Our Proven Solution

Our proven Natural Dermatitis Treatment really works as proven by the many reviews from our happy customers.
Original work URL(s):
  http://www.manukanatural.com/pages/Dermatitis.html

Allegedly infringing URLs:
  0.   http://www.manuka-products.co.nz/index.php?route=cms/article&path=1&article_id=27


SWORN STATEMENTS

I have a good faith belief that use of the copyrighted materials described above as allegedly infringing is not authorized by the copyright owner, its agent, or the law.
[checked]

The information in this notification is accurate, and I swear, under penalty of perjury, that I am the copyright owner or am authorized to act on behalf of the owner of an exclusive right that is allegedly infringed.
[checked]

SIGNATURE
Signed on this date of:
09/15/2011

 
FAQ: Questions and Answers

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Question: What are some of the trademark issues that frequently arise online?

Answer: Trademark issues can arise around use of marks (words or images) in web pages, in domain names, in advertisements or keywords. A few of the most frequently-referenced questions include:

Question: What can be protected as a trademark?

Answer: You can protect

  • names (such as company names, product names)
  • domain names if they label a product or service
  • images
  • symbols
  • logos
  • slogans or phrases
  • colors
  • product design
  • product packaging (known as trade dress)


Question: What exactly are the rights a trademark owner has?

Answer: In the US, trademark rights come from actual use of the mark to label one's services or products or they come from filing an application with the Patent and Trademark Office (PTO) that states an intention to use the mark in future commerce. In most foreign countries, trademarks are valid only upon registration.

There are two trademark rights: the right to use (or authorize use) and the right to register.

The person who establishes priority rights in a mark gains the exclusive right to use it to label or identify their goods or services, and to authorize others to do so. According to the Lanham Act, determining who has priority rights in a mark involves establishing who was the first to use it to identify his/her goods.

The PTO determines who has the right to register the mark. Someone who registers a trademark with the intent to use it gains "constructive use" when he/she begins using it, which entitles him/her to nationwide priority in the mark. However, if two users claim ownership of the same mark (or similar marks) at the same time, and neither has registered it, a court must decide who has the right to the mark. The court can issue an injunction (a ruling that requires other people to stop using the mark) or award damages if people other than the owner use the trademark (infringement).

Trademark owners do not acquire the exclusive ownership of words. They only obtain the right to use the mark in commerce and to prevent competitors in the same line of goods or services from using a confusingly similar mark. The same word can therefore be trademarked by different producers to label different kinds of goods. Examples are Delta Airlines and Delta Faucets.

Owners of famous marks have broader rights to use their marks than do owners of less-well-known marks. They can prevent uses of their marks by others on goods that do not even compete with the famous product.


Question: What implication does alleged confusion have on claims of trademark infringement?

Answer: A mark that is confusingly similar so closely resembles a registered trademark that it is likely to confuse consumers as to the source of the product or service. Consumers could be likely to believe that the product with the confusingly similar mark is produced by the organization that holds the registered mark. Someone who holds a confusingly similar mark benefits from the good will associated with the registered mark and can lure customers to his/her product or service instead. Infringement is determined by whether your mark is confusingly similar to a registered mark. The factors that determine infringement include:

  • proof of actual confusion
  • strength of the established mark
  • proximity of the goods in the marketplace
  • similarity of the marks? sound
  • appearance and meaning
  • how the goods are marketed
  • type of product and how discerning the customer is
  • intent behind selecting the mark
  • likelihood of expansion in the market of the goods


Question: What are the limits of trademark rights?

Answer: There are many limits, including:

  • Fair Use
    There are two situations where the doctrine of fair use prevents infringement:
    1. The term is a way to describe another good or service, using its descriptive term and not its secondary meaning. The idea behind this fair use is that a trademark holder does not have the exclusive right to use a word that is merely descriptive, since this decreases the words available to describe. If the term is not used to label any particular goods or services at all, but is perhaps used in a literary fashion as part of a narrative, then this is a non-commercial use even if the narrative is commercially sold.
    2. Nominative fair use
      This is when a potential infringer (or defendant) uses the registered trademark to identify the trademark holder's product or service in conjunction with his or her own. To invoke this defense, the defendant must prove the following elements:
      • the product or service cannot be readily identified without the mark
      • he/she only uses as much of the mark as is necessary to identify the goods or services
      • he/she does nothing with the mark to suggest that the trademark holder has given his approval to the defendant
  • Parody Use
    Parodies of trademarked products have traditionally been permitted in print and other media publications. A parody must convey two simultaneous -- and contradictory -- messages: that it is the original, but also that it is not the original and is instead a parody.
  • Non-commercial Use
    If no income is solicited or earned by using someone else's mark, this use is not normally infringement. Trademark rights protect consumers from purchasing inferior goods because of false labeling. If no goods or services are being offered, or the goods would not be confused with those of the mark owner, or if the term is being used in a literary sense, but not to label or otherwise identify the origin of other goods or services, then the term is not being used commercially.
  • Product Comparison and News Reporting
    Even in a commercial use, you can refer to someone else?s goods by their trademarked name when comparing them to other products. News reporting is also exempt.
  • Geographic Limitations
    A trademark is protected only within the geographic area where the mark is used and its reputation is established. For federally registered marks, protection is nationwide. For other marks, geographical use must be considered. For example, if John Doe owns the mark Timothy's Bakery in Boston, there is not likely to be any infringement if Jane Roe uses Timothy's Bakery to describe a bakery in Los Angeles. They don't sell to the same customers, so those customers aren't confused.
  • Non-competing or Non-confusing Use
    Trademark rights only protect the particular type of goods and services that the mark owner is selling under the trademark. Some rights to expansion into related product lines have been recognized, but generally, if you are selling goods or services that do not remotely compete with those of the mark owner, this is generally strong evidence that consumers would not be confused and that no infringement exists. This defense may not exist if the mark is a famous one, however. In dilution cases, confusion is not the standard, so use on any type of good or service might cause infringement by dilution of a famous mark.


Question: What is the bare minimum of trademark law that I have to understand to decipher this C&D?

Answer: Your opponent should say that your mark is causing consumer confusion or is likely to cause consumer confusion. Or it should mention it's famousness and complain of dilution or tarnishment. (If the C&D does not say this, then no trademark claim may actually exist, and you can rest assured that your opponent is engaging in scare tactics or has hired a highly incompetent attorney). A mark protects more than identical copying, it extends to anything that is confusingly similar, even if it isn't exactly the same.

Functioning in a quasi-magical talisman-like capacity, trademarks designate the source or quality of goods or services. For this reason, the law protects against confusion in the market place by ensuring that marks on the same or similar products or services are sufficiently different. The law also protects famous marks against dilution of value and tarnishment of the reputation of the goods or services on which it appears or the source of those products, regardless of any confusion.

You can roughly assess the validity of your opponent?s claim of confusion by classifying the marks involved. A trademark can fall into one of 5 categories. It can be: (1) fanciful; (2) arbitrary; (3) suggestive; (4) descriptive; or (5) generic. Not all of these varieties of marks are entitled to the same level, or indeed any level, of trademark protection.

A fanciful mark is a mark someone made up; examples include KODAK or H?AGEN-DAZS. An arbitrary mark is a known term applied to a completely unrelated product or service; for instance, AMAZON.com for an online book-store cum one-stop shopping site or APPLE for computers. Fanciful and arbitrary marks are considered strong marks and garner substantial trademark protection.

A suggestive mark is one that hints at the product, but which requires an act of imagination to make the connection: COPPERTONE for sun tan lotion or PENGUIN for coolers or refrigerators are examples. Suggestive marks are also strong marks and receive protection.

A descriptive mark, predictably, describes the product: HOLIDAY INN describes a vacation hotel and FISH-FRI describes batter for frying fish. Descriptive marks do not receive any trademark protection unless their user has used them in commerce and has built up secondary meaning. "Secondary meaning" occurs when consumers identify the goods or services on which the descriptive term appears with a single source. In other words, if consumers know that HOLIDAY INN hotels are all affiliated with a single source, then the mark has secondary meaning and receives trademark protection.

Finally, generic marks simply designate the variety of goods involved: for example, "cola" used on soft drinks and "perfume" on perfume are both generic terms. Generic marks never receive any trademark protection; they are free for everybody to use. (Keep in mind, though, that "Cola" on a nightclub is arbitrary, and therefore receives protection).

If your opponent is complaining that you have used the word "bakery" for a bake shop or "car" for a car repair shop, then you can safely guess that the c & d is baseless. On the other hand, if your opponent is concerned about the fact that both of you use of the term "Sweet Pickles" on alpaca sweaters, then the c & d may have some merit.

There are a few more wrinkles as well. Some marks are word marks (text only) and others are design marks (images which may or may not include text). Design marks do not provide independent protectin for the text incorporated in the design. So if the mark is only a design mark, it doesn't prevent others from using the text so long as they don't copy the design elements.


Question: What do these registration numbers mean? or Why don

Answer: Do not be led astray by the registration numbers: trademark rights in the United States arise from use of the mark in commerce, not from registering. However, both state and federal law can provide relief from trademark infringement.

If your opponent has registered its mark on the Patent & Trademark Office


Question: What does the "reservation of rights" language mean? What are they "waiving" at me?

Answer: Many C&Ds will say something like, "This letter shall not be deemed to be a waiver of any rights or remedies, which are expressly reserved." This is just legalese for saying, "Even if you do what we ask in this letter, we can still sue you later." The language is standard; do not be alarmed. Litigation is extremely unpleasant, and unless your opponent is irrational (always a distinct possibility, of course), it will not bring litigation after it has obtained what it wants.


Question: What are the limits on dilution?

Answer: The Federal Trademark Dilution Act of 1995 (FTDA, 15 U.S.C. 1125) prohibits the commercial use of a famous mark if such use causes dilution of the distinctive quality of the mark.

A mark may be diluted either by "tarnishment" or "blurring." Tarnishment occurs when someone uses a mark on inferior or unwholesome goods or services. For example a court found that a sexually explicit web site using the domain name "candyland.com" diluted by tarnishment the famous trademark "CANDY LAND" owned by Hasbro, Inc. for its board games.

Blurring occurs when a famous mark or a mark similar to it is used without permission on other goods and services. The unique and distinctive character of the famous mark to identify one source is weakened by the additional use even though it may not cause confusion to the consumer.

The following uses of a famous mark are specifically permitted under the Act:

1) Fair use in comparative advertising to identify the goods or services of the owner of the mark.
2) Noncommercial uses of a mark.
3) All forms of news reporting and news commentary.

In addition, the courts have differed as to what constitutes a "famous" mark under the FTDA. In some cases the courts have said that the famousness requirement limits the Act to a very small number of very widely known marks. Other courts, however, have accepted lesser-known marks as PANAVISION, WAWA and EBONY as being famous and yet others have said that merely being famous in one's product line is sufficient.

Many states also have antidilution laws protecting mark owners.


Question: Is there a DMCA notice-and-takedown requirement for trademark?

Answer: No. The DMCA Safe Harbor and notice-and-takedown requirements apply only to claims of copyright infringement. However, because CDA 230's immunity does not apply to trademark either, Internet hosts may be concerned about possible contributory liability if they do not remove alleged trademark infringement once notified of it.



For more information on Trademark, see the FAQs on Trademark. For more information on Trademarks and Domain Names, see Domain Names and Trademarks.


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Question: Why does a search engine get DMCA takedown notices for materials in its search listings?

Answer: Many copyright claimants are making complaints under the Digital Millennium Copyright Act, Section 512(d), a safe-harbor for providers of "information location tools." These safe harbors give providers immunity from liability for users' possible copyright infringement -- if they "expeditiously" remove material when they get complaints. Whether or not the provider would have been liable for infringement by users' materials it links to, the provider can avoid the possibility of a lawsuit for money damages by following the DMCA's takedown procedure when it gets a complaint. The person whose information was removed can file a counter-notification if he or she believes the complaint was erroneous.

Question: What does a service provider have to do in order to qualify for safe harbor protection?

Answer: In addition to informing its customers of its policies (discussed above), a service provider must follow the proper notice and takedown procedures (discussed above) and also meet several other requirements in order to qualify for exemption under the safe harbor provisions.

In order to facilitate the notification process in cases of infringement, ISPs which allow users to store information on their networks, such as a web hosting service, must designate an agent that will receive the notices from copyright owners that its network contains material which infringes their intellectual property rights. The service provider must then notify the Copyright Office of the agent's name and address and make that information publicly available on its web site. [512(c)(2)]

Finally, the service provider must not have knowledge that the material or activity is infringing or of the fact that the infringing material exists on its network. [512(c)(1)(A)], [512(d)(1)(A)]. If it does discover such material before being contacted by the copyright owners, it is instructed to remove, or disable access to, the material itself. [512(c)(1)(A)(iii)], [512(d)(1)(C)]. The service provider must not gain any financial benefit that is attributable to the infringing material. [512(c)(1)(B)], [512(d)(2)].


Question: What are the provisions of 17 U.S.C. Section 512(c)(3) & 512(d)(3)?

Answer: Section 512(c)(3) sets out the elements for notification under the DMCA. Subsection A (17 U.S.C. 512(c)(3)(A)) states that to be effective a notification must include: 1) a physical/electronic signature of a person authorized to act on behalf of the owner of the infringed right; 2) identification of the copyrighted works claimed to have been infringed; 3) identification of the material that is claimed to be infringing or to be the subject of infringing activity and that is to be removed; 4) information reasonably sufficient to permit the service provider to contact the complaining party (e.g., the address, telephone number, or email address); 5) a statement that the complaining party has a good faith belief that use of the material is not authorized by the copyright owner; and 6) a statement that information in the complaint is accurate and that the complaining party is authorized to act on behalf of the copyright owner. Subsection B (17 U.S.C. 512(c)(3)(B)) states that if the complaining party does not substantially comply with these requirements the notice will not serve as actual notice for the purpose of Section 512.

Section 512(d)(3), which applies to "information location tools" such as search engines and directories, incorporates the above requirements; however, instead of the identification of the allegedly infringing material, the notification must identify the reference or link to the material claimed to be infringing.


Question: Does a service provider have to follow the safe harbor procedures?

Answer: No. An ISP may choose not to follow the DMCA takedown process, and do without the safe harbor. If it would not be liable under pre-DMCA copyright law (for example, because it is not contributorily or vicariously liable, or because there is no underlying copyright infringement), it can still raise those same defenses if it is sued.


Question: How do I file a DMCA counter-notice?

Answer: If you believe your material was removed because of mistake or misidentification, you can file a "counter notification" asking the service provider to put it back up. Chilling Effects offers a form to build your own counter-notice.


For more information on the DMCA Safe Harbors, see the FAQs on DMCA Safe Harbor. For more information on Copyright and defenses to copyright infringement, see Copyright.


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